Dec. 2024, 日本機械学会関東支部2024年度茨城講演会・優秀講演賞【指導学生の受賞】, ホヤ表面ナノ構造の防汚機能メカニズム解明に向けた 摩擦力測定システムの構築（2024年度茨城講演会（2024年8月にて））, 日本機械学会関東支部
大内 椋太,広瀬 裕一,長山 和亮,上杉 薫

Dec. 2024, 日本機械学会関東支部2024年度茨城講演会・優秀講演賞【指導学生の受賞】, がん細胞間の情報伝達を担うナノファイバの 力学特性と機械的役割に関する研究（2024年度茨城講演会（2024年8月にて））, 日本機械学会関東支部
太田 倫汰郎;長山 和亮

Dec. 2024, 日本機械学会関東支部2024年度茨城講演会・優秀講演賞【指導学生の受賞】, 生体組織・細胞の構造支持を司るアクチンストレスファイバの力学特性解析（2024年度茨城講演会（2024年8月にて））, 日本機械学会関東支部
神邊千穂;長山和亮

Sep. 2024, JSMBE Best Research Award 2024, Atomic force microscopy estimation of mechanical properties of tunneling nanotubes in cancer cells, 日本生体医工学会
Rintaro OTA, Kazuaki NAGAYAMA

May 2024, 2023 Journal of Biomechanical Science and Engineering "Graphics of the Year Award", Kazuaki NAGAYAMA, Tatsuya HANZAWA, Akiko SATO: Superficial groove structure in the size of focal adhesion can clarify cell-type-specific differences in force-dependent substrate mechanosensing, Journal of Biomechanical Science and Engineering 18(3): 22-00474, 2023. (https://doi.org/10.1299/jbse.22-00474), JSME
Kazuaki NAGAYAMA, Tatsuya HANZAWA, Akiko SATO:

May 2024, 2023 Journal of Biomechanical Science and Engineering "Papers of the Year Award", Kazuaki NAGAYAMA, Tatsuya HANZAWA, Akiko SATO: Superficial groove structure in the size of focal adhesion can clarify cell-type-specific differences in force-dependent substrate mechanosensing, Journal of Biomechanical Science and Engineering 18(3): 22-00474, 2023. (https://doi.org/10.1299/jbse.22-00474), JSME
Kazuaki NAGAYAMA;Tatsuya HANZAWA;Akiko SATO

Apr. 2024, 日本機械学会関東学生会第63回卒業研究発表講演会 Best Presentation Award【指導学生の受賞】（日本機械学会関東学生会第63回学生員卒業研究発表講演会（2024年3月）に対して）, がん細胞の情報伝達を担う細胞膜ナノチューブの力学特性に関する研究, 日本機械学会関東学生会
太田倫汰郎;長山和亮

Jan. 2024, 日本機械学会 若手研究者フェロー賞【指導学生の受賞】, アクチンストレスファイバのレーザ切断による細胞の損傷修復メカニズム解析,（日本機械学会 M&M2023 材料力学カンファレンス（9月）にて）, 日本機械学会
弓野奎斗,長山和亮

Dec. 2023, 日本機械学会バイオフロンティア講演会・若手優秀講演表彰【指導学生の受賞】, 局所的圧縮で誘発される皮膚線維芽細胞のDNA損傷メカニズム（力学的バイスタンダー効果による細胞がん化の可能性）,, 日本機械学会バイオエンジニアリング部門
廣岡祐仁;中村麻子;長山和亮

Dec. 2023, 日本生体医工学会関東支部若手研究者発表会2023・優秀論文発表賞【指導学生の受賞】, 局所的圧縮による皮膚線維芽細胞の組織的運動とDNA損傷との関わり～力学的バイスタンダー効果の可能性～,, 日本生体医工学会関東支部
廣岡祐仁,中村麻子,長山和亮

Dec. 2023, 日本生体医工学会関東支部若手研究者発表会2023・優秀論文発表賞【指導学生の受賞】, がん細胞間の情報伝達を担うトンネルナノチューブ様構造の力学特性評価,, 日本生体医工学会関東支部
太田倫汰郎;長山和亮

Aug. 2023, 日本機械学会関東支部2023年度茨城講演会・優秀講演賞【指導学生の受賞】, レーザアブレーション法を用いた細胞のマイクロ損傷回復メカニズム解析,, 日本機械学会 関東支部
弓野 奎斗,長山 和亮

Dec. 2022, 日本生体医工学会関東支部若手研究者発表会2022・優秀論文発表賞, 「大橋未来，竹田晃人，長山和亮：機械学習を用いた無染色位相差顕微鏡画像からの細胞核抽出と評価，日本生体医工学会関東支部若手研究者発表会2022, 2022.12.10」に対して, 日本生体医工学会関東支部会
大橋未来,竹田晃人,長山和亮
Japan society

Aug. 2022, 日本機械学会関東支部2022年度茨城講演会・優秀講演賞, 「綿谷直樹，長山和亮：マイクロ溝基板を用いた細胞の形態制御と細胞内部構造の3次元解析，日本機械学会関東支部2022年度茨城講演会, 2022.8.19」に対して，, 日本機械学会 関東支部
池田圭吾,長山和亮
Japan society

Apr. 2022, 2021年度 日本機械学会賞（論文）, 「Nagayama K: Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation, Journal of Biomechanical Science and Engineering 14(4): 19-00364, 2019」 に対して, 日本機械学会
Kazuaki NAGAYAMA
Japan society

Mar. 2022, 日本機械学会関東学生会第60回卒業研究発表講演会 Best Presentation Award, 「廣岡祐仁，上杉 薫，長山和亮：細胞間の力学的相互作用が細胞の紫外線耐性に与える影響～細胞密度および細胞種の違いによる応答変化～，日本機械学会関東学生会第60回卒業研究発表講演会, 2022.3.14」に対して，, 日本機械学会関東学生会
廣岡祐仁,上杉薫,長山和亮
Japan society

Mar. 2022, 日本機械学会関東支部・若手優秀講演賞, 「綿谷直樹，上杉 薫，長山和亮：細胞配列化と繰返引張刺激による血管平滑筋細胞の分化誘導への試み，日本機械学会 関東支部 第28期総会・講演会, 2022.3.15」に対して，, 日本機械学会 関東支部
綿谷直樹,上杉 薫,長山和亮
Japan society

Aug. 2021, 日本機械学会関東支部2021年度茨城講演会・優秀講演賞, 「池田圭吾，上杉薫，長山和亮：細胞の力学応答解析のための顕微鏡下伸展刺激負荷システムの開発，日本機械学会関東支部2021年度茨城講演会, 2021.8.19」に対して，, 日本機械学会 関東支部
池田圭吾,上杉 薫,長山和亮
Japan society

Apr. 2021, 日本機械学会関東支部・若手優秀講演賞, 「村田博教，長山和亮：原子間力顕微鏡を用いた骨芽細胞様細胞の骨分化過程における細胞核の力学特性計測，日本機械学会 関東支部 第27期総会・講演会, 2021.3.15」に対して，, 日本機械学会 関東支部
村田博教,長山和亮
Japan society

Jun. 2020, 2019 Journal of Biomechanical Science and Engineering "Papers of the Year Award", Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation，Journal of Biomechanical Science and Engineering 14(4): 19-00364, 2019, 日本機械学会
Kazuaki NAGAYAMA
Official journal

Jun. 2020, 2019 Journal of Biomechanical Science and Engineering "Graphics of the Year Award", Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation，Journal of Biomechanical Science and Engineering 14(4): 19-00364, 2019, 日本機械学会
Kazuaki NAGAYAMA
Official journal

Sep. 2017, 2016 Journal of Biomechanical Science and Engineering "Graphics of the Year Award", Dynamics of actin filaments of MC3T3-E1 cells during adhesion process to substrate，Journal of Biomechanical Science and Engineering 11-2, 15-00637, 2016, 日本機械学会
Junking WANG;Shukei SUGITA;Kazuaki NAGAYAMA;Takeo MATSUMOTO
Official journal

Sep. 2017, 2016 Journal of Biomechanical Science and Engineering "Papers of the Year Award", Dynamics of actin filaments of MC3T3-E1 cells during adhesion process to substrate，Journal of Biomechanical Science and Engineering 11-2, 15-00637, 2016, 日本機械学会
Junking WANG;Shukei SUGITA;Kazuaki NAGAYAMA;Takeo MATSUMOTO
Official journal

Mar. 2013, 2012 Journal of Biomechanical Science and Engineering "Papers of the Year Award", Dynamic Changes of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate: Tensional Homeostasis of Aortic Smooth Muscle Cells，Journal of Biomechanical Science and Engineering 7, pp. 130-140, 2012, 日本機械学会
Kazuaki NAGAYAMA;Akifumi ADACHI;Takeo MATSUMOTO

Mar. 2013, 2012 Journal of Biomechanical Science and Engineering "Graphics of the Year Award", Dynamic Changes of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate: Tensional Homeostasis of Aortic Smooth Muscle Cells，Journal of Biomechanical Science and Engineering 7, pp. 130-140, 2012, 日本機械学会
Kazuaki NAGAYAMA;Akifumi ADACHI;Takeo MATSUMOTO

Apr. 2010, 2009年度 日本機械学会賞（論文）, 日本機械学会
Kazuaki NAGAYAMA;Akira TSUGAWA;Takeo MATSUMOTO

Apr. 2010, 2009年度 日本機械学会賞（論文）, Tensile Properties of Cultured Aortic Smooth Muscle Cells Obtained in a quasi-in situ Tensile Test with Thermoresponsive Gelatin, Journal of Biomechanical Science and Engineering, Vol.1, No. 1, pp. 256-267, (2006), 日本機械学会
Kazuaki NAGAYAMA;Akira TSUGAWA and Takeo MATSUMOTO

Jan. 2009, 2008年度 日本機械学会バイオエンジニアリング部門 第17回 瀬口賞, 日本機械学会バイオエンジニアリング部門
長山和亮

Apr. 2007, 平成18年度 日本生体医工学会 研究奨励賞・阪本研究刊行助成賞・阿部賞, マイクロパターニング技術を用いた細胞の形状・配向制御ならびに力学応答解析, 第45回日本生体医工学会大会（2006.05.15-17, 福岡）に対して, 日本生体医工学会
長山和亮

Apr. 2005, 2004年度 日本機械学会賞（論文）, 細胞の力学特性計測のためのレーザ顕微鏡複合型原子間力顕微鏡(AFM)システムの開発, 日本機械学会論文集C編70(691), 128-134 (2004), 日本機械学会
長山和亮;佐々木実;羽根一博;佐藤正明;松本健郎

〔Major achievements〕Downregulation of Nesprin1 by Runx2 deficiency is critical for the development of skeletal laminopathy-like pathology
Akiko Saito; Kazuaki Nagayama; Hiroyuki Okada; Shoko Onodera; Natsuko Aida; Takashi Nakamura; Takashi Sawada; Hironori Hojo; Shigeaki Kato; Toshifumi Azuma, Runx2 is a master regulator of bone formation, and its dysfunction causes cleidocranial dysplasia (CCD) in humans. When iPS cells were generated from patients with CCD and Runx2-deficient iPS cells were generated using gene-editing techniques, abnormal laminopathy-like nuclei were observed. Runx2-deficient cells showed reduced Lamin A/C expression, but not protein levels. However, in Runx2-deficient cells, both the gene expression and protein levels of Nesprin1 were reduced, perinuclear actin fibers were sparser, and nuclear stiffness was reduced. Forced expression of Lamin A/C increased nuclear stiffness but did not improve nuclear morphology. In contrast, the induction of Nesprin1 expression alone normalized nuclear stiffness and restored nuclear morphology and perinuclear actin distribution. In Runx2-null cells, mechanical stress-induced phosphorylation of emerin was not observed. In contrast, forced expression of Nesprin1 in Runx2-null cells resulted in phosphorylation of emerin, indicating the restoration of intracellular tension. These observations were confirmed by atomic force microscopy. Therefore, the intracellular tension was inferred to pull the nuclear membrane into its normal shape. CUT&RUN assay and single RNA-seq analysis showed that an aberrant nuclear membrane caused loss of nuclear lamina gene regulation machinery, making the progression of normal osteogenic differentiation impossible; however, supplementation with Nesprin1 restored gene regulation mechanisms and promoted preosteoblast formation with normal nuclear morphology. Nesprin1 expression induced by Runx2 is essential for epigenetic regulation of the nuclear lamina. We propose CCD as a type of laminopathy involving defective expression of Nesprin1 regulated by Runx2., Proceedings of the National Academy of Sciences
Proceedings of the National Academy of Sciences of the United States of America（PNAS）, 10 Apr. 2025, [Reviewed]

〔Major achievements〕Effect of the cell orientation angle on the nucleus of a cultured vascular smooth muscle cell subjected to uniaxial stretching: A finite element analysis
Atsutaka Tamura; Shoma Uehara; Yasuhiro Tanabe; Kazuaki Nagayama, Last
ASME Journal of Engineering and Science in Medical Diagnostics and Therapy., Mar. 2025, [Reviewed]

〔Major achievements〕Laser nanodissection for intracellular actin stress fibers and analysis of the severed fiber retraction and regeneration behavior
Chiho KAMBE; Kazuaki NAGAYAMA, Last
Transactions of the JSME, Mar. 2025, [Reviewed]

〔Major achievements〕Atomic force microscopy estimation of mechanical properties of tunneling nanotubes in cancer cells
Rintaro OTA; Kazuaki NAGAYAMA, Last
Advanced Biomedical Engineering, Feb. 2025, [Reviewed]

Changes in the mechanical environment of the nucleus with cell crowding and its effects on DNA damage resistance
Kazuaki Nagayama; Yuto Hirooka, Lead
Journal of Biosciences and Medicines, Jan. 2025, [Reviewed]

〔Major achievements〕Dedifferentiation- and aging-induced loss of mechanical contractility and polarity in vascular smooth muscle cells: Heterogeneous changes in macroscopic and microscopic behavior of cells in serial passage culture
Kazuaki Nagayama; Kenzo Nogami; Shunta Sugano; Miku Nakazawa, Lead, Elsevier BV
Journal of the Mechanical Behavior of Biomedical Materials, Dec. 2024, [Reviewed]

〔Major achievements〕Extraction and evaluation of cell nuclei images in label-free phase contrast microscopy enabled by machine learning using a data analysis platform Usiigaci
Kazuaki NAGAYAMA; Miku OHASHI; Hotaka DANGI; Koujin TAKEDA, Lead, Japan Society of Mechanical Engineers
Transactions of the JSME (in Japanese), Nov. 2024, [Reviewed]

〔Major achievements〕Mechanical Trapping of the Cell Nucleus Into Microgroove Concavity But Not On Convexity Induces Cell Tissue Growth and Vascular Smooth Muscle Differentiation
Kazuaki Nagayama; Naoki Wataya, Lead, Springer Science and Business Media LLC
Cellular and Molecular Bioengineering, 22 Oct. 2024, [Reviewed]

Suppression of cell traction force and enhanced force polarity are key factors in vascular smooth muscle cell differentiation induced by low serum culture
Kazuaki Nagayama; Harunobu Tatsuno, Lead
Journal of Biosciences and Medicines, Aug. 2024, [Reviewed]

〔Major achievements〕Micro tensile tester measurement of biomechanical properties and adhesion force of microtubule-polymerization-inhibited cancer cells
Kaoru Uesugi; Shota Obata; Kazuaki Nagayama, Last, Elsevier BV
Journal of the Mechanical Behavior of Biomedical Materials, Aug. 2024, [Reviewed]

〔Major achievements〕Deformation and Trapping of Cell Nucleus Using Micropillar Substrates Possibly Affect UV Radiation Resistance of DNA
Kazuaki Nagayama; Chiaki Sagawa; Akiko Sato, Lead, DNA damage induced by the ultraviolet (UV) light, which affects adversely on genome stability, causes many kinds of diseases. Thus, a biochemical or biomechanical method in DNA damage protection is well required. In the present study, we investigated the effects of mechanical factors, such as deformation of cell nucleus using polydimethylsiloxane (PDMS)-based microfabricated array of micropillars, on UV radiation resistance of DNA in cultured cells. The epithelial-like cells spread normally in the spaces between micropillars and their nuclei showed remarkable deformation and appeared to be “trapped” mechanically on the array of pillars. We found that the UV radiation-induced DNA damage estimated by the fluorescent intensity of the phospho-histone γ-H2AX, was significantly inhibited with the nucleus deformation on the pillars. The result indicates that the inhibition of UV radiation-induced DNA damages might be resulted from structural change of DNA caused by the mechanical stress of the cell nucleus on the micropillars., Fuji Technology Press Ltd.
Journal of Robotics and Mechatronics, 20 Oct. 2023, [Reviewed]

〔Major achievements〕Partial endothelial-to-mesenchymal transition (EndMT) mediated by HIF-induced CD45 in neointima formation upon carotid artery ligation,
Yamashiro Y; Ramirez K; Nagayama K; Hattori N; Liu Y; Matsunaga S; Tomita S; Kubota Y; Yanagisawa H, AIMS: Endothelial-to-mesenchymal transition (EndMT) is a fundamental process in vascular remodeling. However, the precise regulatory mechanism of vascular remodeling during neointima formation and source of neointima cells are not entirely understood. METHODS AND RESULTS: To investigate the origin of neointima cells and their relevance to vascular wall remodeling, we used an EC-specific lineage tracing system (VE-Cadherin (Cdh5)-BAC-CreERT2 mice) and carotid artery ligation model, and showed evidence that resident endothelial cells (ECs) transdifferentiate into neointima cells with expression of CD45. During the early stages of neointima formation, ECs transiently expressed CD45, a hematopoietic marker, accompanied by a host of EndMT markers, and CD31 and αSMA were prominently expressed in developing neointima. In vitro, CD45-positive EndMT was induced by stabilization of HIF1α with cobalt chloride or with a VHL inhibitor in human primary ECs, which mimicked the hypoxic condition of the ligated artery, and promoted the formation of an integrin α11-SHARPIN complex. Notably, a CD45 phosphatase inhibitor disrupted this complex, thereby destabilizing cell-cell junctions. Deletion of Hif1α in ECs suppressed expression of CD45 and EndMT markers, and ameliorated neointima formation. CONCLUSIONS: These results suggest that the HIF-induced CD45 expression is normally required for the retention of an EC fate and cell-cell junctions, CD45-positive EndMT (termed as "partial EndMT") contributes to neointima formation and vascular wall remodeling. TRANSLATIONAL PERSPECTIVE: Our study identifies ECs as an origin of neointima, which is generated through partial EndMT and provides new evidence to the long-debated origin of neointimal cells after vascular injury. The ectopic CD45 expression in ECs is involved in the maintenance of endothelial cell-cell junction during EndMT process. Our data suggests a potential therapeutic strategy targeting the EndMT process to control neointima formation.
Cardiovascular Research., 01 Jun. 2023, [Reviewed]

〔Major achievements〕Inducement of cell tissue arrangement and vascular smooth muscle differentiation,Abstract using micro-grooved concaves,
綿谷直樹,長山和亮, Last
日本機械学会論文集., 25 Mar. 2023, [Reviewed]

〔Major achievements〕Superficial groove structure in the size of focal adhesion can clarify cell-type-specific differences in force-dependent substrate mechanosensing,
Kazuaki NAGAYAMA; Tatsuya HANZAWA; Akiko SATO, Lead
Journal of Biomechanical Science and Engineering., 21 Mar. 2023, [Reviewed]

〔Major achievements〕Actin crosslinking by α-actinin averts viscous dissipation of myosin force transmission in stress fibers,
Katsuta H; Okuda S; Nagayama K; Machiyama H; Kidoaki S; Kato M; Sokabe M; Miyata T; Hirata H, Contractile force generated in actomyosin stress fibers (SFs) is transmitted along SFs to the extracellular matrix (ECM), which contributes to cell migration and sensing of ECM rigidity. In this study, we show that efficient force transmission along SFs relies on actin crosslinking by α-actinin. Upon reduction of α-actinin-mediated crosslinks, the myosin II activity induced flows of actin filaments and myosin II along SFs, leading to a decrease in traction force exertion to ECM. The fluidized SFs maintained their cable integrity probably through enhanced actin polymerization throughout SFs. A computational modeling analysis suggested that lowering the density of actin crosslinks caused viscous slippage of actin filaments in SFs and, thereby, dissipated myosin-generated force transmitting along SFs. As a cellular scale outcome, α-actinin depletion attenuated the ECM-rigidity-dependent difference in cell migration speed, which suggested that α-actinin-modulated SF mechanics is involved in the cellular response to ECM rigidity.
iScience., 01 Feb. 2023, [Reviewed]

〔Major achievements〕Changes in the intra- and extra- mechanical environment of the nucleus in Saos-2 osteoblastic cells during bone differentiation process:Nuclear shrinkage and stiffening in cell differentiation,
Nagayama K; Kodama F; Wataya N; Sato A; Matsumoto T, Lead
Journal of the Mechanical Behavior of Biomedical Materials., 01 Feb. 2023, [Reviewed]

〔Major achievements〕Polarized light retardation analysis allows for the evaluation of tension in individual stress fibers,
Sugita S; Hozaki M; Matsui ST; Nagayama K; Deguchi S; Nakamura M
Biochemical and Biophysical Research Communications., 15 Sep. 2022, [Reviewed]

〔Major achievements〕Cell type-specific orientation and migration responses for a microgrooved surface with shallow grooves,
Nagayama K; Hanzawa T, Lead
Bio-Medical Materials and Engineering., 09 Sep. 2022, [Reviewed]

〔Major achievements〕C9orf72-derived proline:arginine poly-dipeptides modulate cytoskeleton and mechanical stress response
Shiota T; Nagata R; Kikuchi S; Nanaura H; Matsubayashi M; Nakanishi M; Kobashigawa S; Isozumi N; Kiriyama T; Nagayama K; Sugie K; Yamashiro Y; Mori E, Proline:arginine (PR) poly-dipeptides from the GGGGCC repeat expansion in C9orf72 have cytotoxicity and bind intermediate filaments (IFs). However, it remains unknown how PR poly-dipeptides affect cytoskeletal organization and focal adhesion (FA) formation. Here, we show that changes to the cytoskeleton and FA by PR poly-dipeptides result in the alteration of cell stiffness and mechanical stress response. PR poly-dipeptides increased the junctions and branches of the IF network and increased cell stiffness. They also changed the distribution of actin filaments and increased the size of FA and intracellular calcium concentration. PR poly-dipeptides or an inhibitor of IF organization prevented cell detachment. Furthermore, PR poly-dipeptides induced upregulation of mechanical stress response factors and led to a maladaptive response to cyclic stretch. These results suggest that the effects of PR poly-dipeptides on mechanical properties and mechanical stress response may serve as a pathogenesis of C9orf72-related neurodegeneration., Frontiers Media SA
Frontiers Cell and Developmental Biology,, 09 Mar. 2022, [Reviewed]

〔Major achievements〕Keeping a Clean Surface under Water: Nanoscale Nipple Array Decreases Surface Adsorption and Adhesion Forces
Uesugi K; Nagayama K; Hirose E, While nanoscale nipple arrays are expected to reduce light reflection and/or dust contamination in some insects, similar structures have been reported in various marine invertebrates. To evaluate the anti-contamination property of the structure in aquatic regimes, we measured the adsorption and adhesion forces on the flat surface and MOSMITE™ (Mitsubishi Chemical Corporation, Tokyo, Japan), a synthetic material mimicking the nipple array, under water. A small force toward the surface occurred when the probe approached the substrate surface. This adsorption force was significantly smaller on MOSMITE™ than on the flat surface. The adhesion force toward the surface occurred when the probe was detached from the surface, and it was also significantly smaller on MOSMITE™ than on the flat surface. The adhesion force in the air was much greater than the force under water, and the force was also significantly smaller on MOSMITE™ than on the flat surface. In the aquatic regime, the nipple array provides less adsorption/adhesion properties for the surface and thus, the organisms would have less contamination of microparticles on their body surface. As the adsorption and adhesion forces are also involved in the attachment of cells, tissue, and larvae, less adhesive body surfaces should be beneficial for survival in aquatic environments, as well as land environments., MDPI AG
Journal of Marine Science and Engineering,, 05 Jan. 2022, [Reviewed]

細胞への静水圧刺激負荷による紫外線誘導DNA損傷の抑制効果
上杉薫,佐藤賢也,長山和亮, Last
実験力学, 30 Sep. 2021, [Reviewed]

〔Major achievements〕A loss of nuclear–cytoskeletal interactions in vascular smooth muscle cell differentiation induced by a micro-grooved colla-gen substrate enabling the modeling of an in vivo cell ar-rangement
Nagayama K, Lead
Bioengineering,, 12 Sep. 2021, [Reviewed]

〔Major achievements〕弾性マイクロピラーと短パルスレーザ切断システムを使った血管構成細胞の収縮能力の定量解析,－細胞の脱分化と老化に伴うアクチン細胞骨格の張力の変化－　　　　　　　　　　　　　　　
長山和亮; 野上謙三; 菅野隼多, Lead
精密工学会誌, 11 Dec. 2020, [Reviewed]

〔Major achievements〕Development of an in-process micro tensile tester and its application for measurement of the mechanical properties and adhesion forces of cells (Quantitative analysis of a cancer cell stiffness and adhesion forces),
小幡祥太; 長山和亮, Last
日本機械学会論文集., 07 Dec. 2020, [Reviewed]

〔Major achievements〕Analysis of vascular smooth muscle cell and HeLa cell migration on the microgroove substrate (Cell type differences of the mechanical sensing for microgrooved surfaces)
半沢達也; 長山和亮, Last
日本機械学会論文集., 02 Dec. 2020, [Reviewed]

〔Major achievements〕Macroscopic and microscopic analysis of the mechanical properties and adhesion force of cells using a single cell tensile test and atomic force microscopy,
Nagayama K; Ohata S; Obata S; Sato A, Lead
Journal of the Mechanical Behavior of Biomedical Materials,, 15 Jun. 2020, [Reviewed]

〔Major achievements〕Moderate Substrate Stiffness Induces Vascular Smooth Muscle Cell Differentiation Through Cellular Morphological and Tensional Changes,
Nagayama K; Nishimiya K, Lead
Bio-Medical Materials and Engineering., 15 May 2020, [Reviewed]

〔Major achievements〕Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling.
Yoshito Yamashiro; Bui Quoc Thang; Karina Ramirez; Seung Jae Shin; Tomohiro Kohata; Shigeaki Ohata; Tram Anh Vu Nguyen; Sumio Ohtsuki; Kazuaki Nagayama; Hiromi Yanagisawa, The extracellular matrix (ECM) initiates mechanical cues that activate intracellular signaling through matrix-cell interactions. In blood vessels, additional mechanical cues derived from the pulsatile blood flow and pressure play a pivotal role in homeostasis and disease development. Currently, the nature of the cues from the ECM and their interaction with the mechanical microenvironment in large blood vessels to maintain the integrity of the vessel wall are not fully understood. Here, we identified the matricellular protein thrombospondin-1 (Thbs1) as an extracellular mediator of matrix mechanotransduction that acts via integrin αvβ1 to establish focal adhesions and promotes nuclear shuttling of Yes-associated protein (YAP) in response to high strain of cyclic stretch. Thbs1-mediated YAP activation depends on the small GTPase Rap2 and Hippo pathway and is not influenced by alteration of actin fibers. Deletion of Thbs1 in mice inhibited Thbs1/integrin β1/YAP signaling, leading to maladaptive remodeling of the aorta in response to pressure overload and inhibition of neointima formation upon carotid artery ligation, exerting context-dependent effects on the vessel wall. We thus propose a mechanism of matrix mechanotransduction centered on Thbs1, connecting mechanical stimuli to YAP signaling during vascular remodeling in vivo.
Proceedings of the National Academy of Sciences of the United States of America, 05 May 2020

〔Major achievements〕Mechanical Stress to Cell Nucleus Inhibits Proliferation and Differentiation of Vascular Smooth Muscle Cells
Nagayama K, Lead
Journal of Biosciences and Medicines, 02 May 2020, [Reviewed]

〔Major achievements〕Cyclic stretch-induced mechanical stress to the cell nucleus inhibits ultraviolet radiation-induced DNA damage，
Nagayama K; Fukuei T, Lead
Biomechanics and Modeling in Mechanobiology，, 15 Apr. 2020, [Reviewed]

〔Major achievements〕Directional dependence of cyclic stretch-induced cell migration ,in wound healing process of monolayer cells，
Nagayama K; Suzuki Y; Fujiwara D, Lead
Advanced Biomedical Engineering，, 05 Nov. 2019, [Reviewed]

〔Major achievements〕Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation，
Nagayama K, Lead
Journal of Biomechanical Science and Engineering，, 02 Oct. 2019, [Reviewed]

〔Major achievements〕顕微鏡下マイクロ引張試験機による血管構成細胞のスティフネスと接着力の定量解析 (細胞の硬さと接着力の実測）,
長山和亮; 大畠成暁, Lead
精密工学会誌．, 10 Sep. 2019, [Reviewed]

〔Major achievements〕Shape-dependent regulation of differentiation lineages of bone marrow-derived cells under cyclic stretch,
Maeda E; Atsumi Y; Ishiguro M; Nagayama K; Matsumoto T
Journal of Biomechanics，, 21 Aug. 2019, [Reviewed]

〔Major achievements〕基質弾性率の変化が血管平滑筋細胞の形態・張力・分化に及ぼす影響（原子間力顕微鏡を用いた細胞の表面形態・張力変化の解析）,
長山和亮; 西宮昂平, Lead
日本機械学会論文集., 28 Nov. 2018, [Reviewed]

〔Major achievements〕A novel micro-grooved collagen substrate for inducing vascular smooth muscle differentiation through cell tissue arrangement and nucleus remodeling,
Nagayama K; Uchida K; Sato A, Lead
Journal of the Mechanical Behavior of Biomedical Materials,, 21 Oct. 2018, [Reviewed]

〔Major achievements〕A Finite Element Bendo-Tensegrity Model of Eukaryotic Cell,
Bansod YD; Matsumoto T; Nagayama K; Bursa J
Journal of Biomechanical Engineering,, 01 Oct. 2018, [Reviewed]

Si含有リン酸カルシウム薄膜の作製と細胞接着性評価,　　　　　　　　　　　　　　　
越生康寛; 長山和亮; 後藤哲哉; 尾関和秀
バイオインテグレーション学会誌., 28 Sep. 2018, [Reviewed]

〔Major achievements〕Direct application of mechanical stimulation to cell adhesion sites using a novel magnetic-driven micropillar substrate,
Nagayama K; Inoue T; Hamada Y; Sugita S; Matsumoto T., Lead
Biomedical Microdevices,, 26 Sep. 2018, [Reviewed]

〔Major achievements〕Ex-vivo observation of calcification process in chick tibia slice: Augmented calcification along collagen fiber orientation in specimens subjected to static stretch,
Maeda E; Ichikawa K; Murase K; Nagayama K; Matsumoto T
Journal of Biomechanics,, 18 Jun. 2018, [Reviewed]

Analysis of the effect of the size of three-dimensional micro-geometric structures on physical adhesion phenomena using microprint technique,
Oota-Ishigaki A; Masuzawa T; Nagayama K, Last
The International Journal of Artificial Organs,, 15 May 2018, [Reviewed]

A novel patterned magnetic micropillar array substrate for analysis of cellular mechanical responses
Kazuaki Nagayama; Takuya Inoue; Yasuhiro Hamada; Takeo Matsumoto, Traction forces generated at cellular focal adhesions (FAs) play an essential role in regulating various cellular functions. These forces (1-100 nN) can be measured by observing the local displacement of a flexible substrate upon which cells have been plated. Approaches employing this method include using microfabricated arrays of poly(dimethylsiloxane) (PDMS) micropillars that bend by cellular traction forces. A tool capable of applying a force to FAs independently, by actively moving the micropillars, should become a powerful tool to delineate the cellular mechanotransduction mechanisms. Here, we developed a patterned magnetic micropillar array PDMS substrate that can be used for the mechanical stimulation of cellular FM and the measurement of associated traction forces. The diameter, length, and center-to-center spacing of the micropillars were 3, 9, and 9 gm, respectively. Iron particles were embedded into the micropillars, enabling the pillars to bend in response to an external magnetic field, which also controlled their location on the substrate. Applying a magnetic field of 0.3 T bent the pillars by 4 gm and allowed transfer of external forces to the actin cytoskeleton through FM formed on the pillar top. Using this approach, we investigated the traction force changes in cultured aortic smooth muscle cells (SMCs) after local compressive stimuli to release cell pretension. The mechanical responses of SMCs were roughly classified into two types: almost a half of the cells showed a little decrease of traction force at each pillar following compressive stimulation, although cell area increased significantly; and the rest showed the opposite, with increased forces and a simultaneous decrease in area. The traction forces of SMCs fluctuated markedly during the local compression. The root mean square of traction forces significantly increased during the compression, and returned to the baseline level after its release. These results suggest that the fluctuation of forces may be caused by active reorganization of the actin cytoskeleton and/or its dynamic interaction with myosin molecules. Thus, our magnetic micropillar substrate would be useful in investigating the mechanotransduction mechanisms of cells. (C) 2017 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, Dec. 2017, [Reviewed]

A Novel Apparatus for the Multifaceted Evaluation of Arterial Function Through Transmural Pressure Manipulation
Toshiyuki Yaguchi; Yalin Cong; Kenji Shimo; Takahiro Kurokawa; Shukei Sugita; Kazuaki Nagayama; Hiroshi Masuda; Takeo Matsumoto, A novel apparatus for the multifaceted evaluation of artery function was developed. It measures endothelial and smooth muscle functions and the pressure-strain elastic modulus (E (p)). A rigid airtight chamber with an ultrasound probe was attached to the upper arm to manipulate the transmural pressure of the brachial artery. Endothelial function was measured via a standard flow-mediated dilation (FMD) protocol. Smooth muscle function was evaluated via a myogenic contraction of the artery following the application of negative pressure to the chamber and was named pressure-mediated contraction (PMC). E (p) was obtained by measuring the instantaneous increase in the artery diameter following the negative pressure application. The PMC and FMD values had a significant negative correlation with age, indicating that the age-related decrease in FMD is caused by the decay of endothelial and smooth muscle function. A consideration of PMC may help improve the accuracy of artery function measurement. E (p) in subjects aged > 40 years was found to be significantly higher in the supra-physiological pressure range than in the physiological one (p = 0.02); this did not occur in younger subjects. Artery stiffening may begin in the supra-physiological range, and this stiffness may also be used for the diagnosis of atherosclerosis., SPRINGER
ANNALS OF BIOMEDICAL ENGINEERING, Jun. 2017, [Reviewed]

〔Major achievements〕Effects of cyclic compression on the mechanical properties and calcification process of immature chick bone tissue in culture
Eijiro Maeda; Masashi Nakagaki; Katsuhisa Ichikawa; Kazuaki Nagayama; Takeo Matsumoto, Contribution of mechanical loading to tissue growth during both the development and post-natal maturation is of a particular interest, as its understanding would be important to strategies in bone tissue engineering and regenerative medicine. The present study has been performed to investigate how immature bone responds to mechanical loading using an ex vivo culture system. A slice of the tibia, with the thickness of 3 mm, was obtained from 0-day-old chick. For the ex vivo culture experiment in conjunction with cyclic compressive loading, we developed a custom-made, bioreactor system where both the load and the deformation applied to the specimen was recorded. Cyclic compression, with an amplitude of 0.3 N corresponding to 1 to 2% compressive strain, was applied to immature bone specimen during a 3-day culture period at an overall loading rate 3–4 cycles/min, in the presence of β-glycerol phosphate and dexamethasone in culture medium. The stress-strain relationship was obtained at the beginning and the end of the culture experiment. In addition, analyses for alkaline phosphate release, cell viability and tissue calcification were also performed. It was exhibited that elastic moduli of bone slices were significantly elevated at the end of the 3-day culture in the presence of cyclic compression, which was a similar phenomenon to significant elevation of the elastic moduli of bone tissue by the maturation from 0-day old to 3-day old. By contrast, no significant changes in the moduli were observed in the absence of cyclic compression or in deactivated, cell-free samples. The increases in the moduli were coincided with the increase in calcified area in the bone samples. It was confirmed that immature bone can respond to compressive loading in vitro and demonstrate the growth of bone matrix, similar to natural, in vivo maturation. The elevation of the elastic moduli was attributable to the increased calcified area and the realignment of collagen fibers parallel to the loading direction. The ex vivo loading system established here can be further applied to study responses to mechanical loading in osteogenesis as well as callus maturation for better understanding of factors to consider in successful bone regeneration with mechanical factors., Elsevier Inc
Bone Reports, 01 Jun. 2017, [Reviewed]

〔Major achievements〕The effects of the mechanical trapping of the nucleus on cellular UV resistance using a micropillar substrate
Chiaki SAGAWA and Kazuaki NAGAYAMA., Lead,

DNA damage induced by the radiation, including ultraviolet (UV) light, exerts adverse effects on genome stability, alters the normal state of life, and causes many kinds of diseases. Thus, a biochemical or biomechanical method in DNA damage repair and protection is well required. Hear we investigated the effects of mechanical factors, such as mechanical deformation of the nucleus, on UV radiation resistance of DNA in epithelial-like cells derived from Xenopus laevis (XTC-YF). XTC-YF cells spread normally in the spaces between micropillars whose diameter, length, and center to center spacing was 3, 9, and 9 μm, respectively. Their nuclei showed remarkable deformation and appeared to be "trapped" mechanically on the array of pillars. We compared the cells cultured on the normal flat substrates and on the pillar substrates and found that the UV radiation-induced DNA damage estimated by the fluorescent intensity of the phospho-histone γ-H2A.X, was significantly inhibited in the cells cultured on the pillar substrates. The significant positive correlation was observed between fluorescent intensity of intranuclear DNA and γ-H2A.X in the cells cultured on the flat substrates following UV irradiation, while in the cells on the pillar substrate, their correlation became lower. These results indicate that the inhibition of UV radiation-induced DNA damages might be resulted from structural change of DNA caused by the mechanical stress of the nucleus of the cells on the pillars. Our study first demonstrated the nuclear stress-induced inhibition of DNA damages in living cells.

, 日本機械学会．
日本機械学会論文集．, May 2017, [Reviewed]

Real-time in situ observation of immature bone tissue subjected to mechanical loading in culture
Maeda Eijiro; Ichikawa Katsuhisa; Murase Kohei; Nagayama Kazuaki; Matsumoto Takeo
IEEE Conference Proceedings, 2017

〔Major achievements〕Differences in the Mechanical Properties of the Developing Cerebral Cortical Proliferative Zone between Mice and Ferrets at both the Tissue and Single-Cell Levels．
Arata Nagasaka; Tomoyasu Shinoda; Takumi Kawaue; Makoto Suzuki; Kazuaki Nagayama; Takeo Matsumoto; Naoto Ueno; Ayano Kawaguchi and Takaki Miyata., Frontiers Media SA
Front. Cell Dev. Biol.,, 25 Nov. 2016, [Reviewed]

Tensile properties of smooth muscle cells, elastin, and collagen fibers
Takeo Matsumoto; Shukei Sugita; Kazuaki Nagayama, Artery walls change their dimensions as well as mechanical properties adaptively in response to mechanical stimulation. Because these responses are caused by the vascular smooth muscle cells (VSMCs) in the media, detailed understanding of the mechanical environment of the VSMCs is indispensable to know the mechanism of the adaptation. Artery wall has been often assumed to be homogenous in conventional mechanical analyses from macroscopic viewpoint. At a microscopic level, however, it is highly heterogeneous, and conventional mechanical analyses using homogeneous models are far from satisfactory to estimate the mechanical environment of the VSMCs. Thus, the mechanical properties of each element composing the artery wall, i.e., VSMCs, elastin, and collagen fibers, should be measured directly. In this chapter, we first introduce the experimental techniques used for the tensile testing of tissues and cell at a microscopic scale and review the tensile properties of VSMCs in detail, and then, those of elastin and collagen fibers. In contrast to elastin and collagen fibers that are simple passive materials, VSMCs are alive and their mechanical properties are highly complicated. Their mechanical properties are reviewed from the viewpoints of smooth muscle contraction, anisotropy in cytoskeletal structure, and viscoelasticity., Springer Japan
Vascular Engineering: New Prospects of Vascular Medicine and Biology with a Multidiscipline Approach, 01 Jan. 2016, [Reviewed]

Dynamics of actin filaments of MC3T3-E1 cells during adhesion process to substrate
Junfeng Wang; Shukei Sugita; Kazuaki Nagayama; Takeo Matsumoto, In order to determine how cells change their morphology during adhesion process to a substrate, we focused on the actin cytoskeleton and investigated its morphological change along with that of the whole cell during adhesion process. An osteoblastic cell line MC3T3-E1 was used as the test model. We plated cells whose cell cycle had been synchronized by serum starvation on fibronectin-coated glass plate and cultured them for 10 min to 24 h. We then stained their F-actin and nucleus and observed them with a fluorescent microscope for cell area and shape index and 2D parameters for actin morphology, and with a laser scanning microscope for 3D morphology of actin and nucleus. In the beginning of adhesion, the trypsinized cells were round and their nuclei were surrounded uniformly by thick layer of actin. The actin layer in the upper side became actin aggregate (AA) and lower side dense peripheral band (DPB) in 30 min. The upper AA then became smaller and finally to actin filaments (AFs) spanning the cell top. The DPB expanded and finally became AFs on cell bottom by 1 h. The nucleus becomes flattened possibly due to compression by the cell membrane caused by the expansion of the DPB in the early stage of adhesion. In the later stage of adhesion, the number of AFs continuously increased and nucleus became flattened more and more until 12 h. This may be caused by the increase in the top AFs that may compress the nucleus. Cells become more elongated in response to further alignment of AFs until 12 h. These results indicate that change in AFs during adhesion process is complicated not only temporally but also spatially., Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 2016, [Reviewed]

Cyclic stretch-induced morphological changes of the nucleus possibly improve the ultraviolet radiation resistance in cells
Kazuaki Nagayama; Tomohiro Fukuei, Ultraviolet (UV) radiation exerts adverse effects on genome stability, alters the normal state of life, and causes many diseases by inducing DNA damage. Although mechanical stimulation, such as stretching and compressing, to cells has beneficial effects in the prevention and treatment of diseases, whether it influences the nuclear morphology and/or intranuclear functions associated with DNA damage remains unknown. In this study, we investigated the effects of mechanical stimulation by cyclic stretching on nuclear morphology and resistance to UV radiation of DNA in epithelial-like cells derived from Xenopus laevis (XTC-YF). Cells adhering to silicone membranes were subjected to 10％ cyclic uniaxial stretch at a frequency of 0.5 Hz for 12 h. We observed that the intracellular actin cytoskeleton and nucleus became elongated and aligned with the direction of zero normal strain (~62� with respect to the stretch direction) following the cyclic stretch exposure. The fluorescent intensity of intranuclear DNA, which represents the DNA density, increased significantly. The intercellular tension, assessed by the retraction of cells upon detachment from the silicone membrane, also increased following the cyclic stretch exposure. Furthermore, UV radiation-induced DNA damage, estimated by the fluorescent intensity of phospho-histone γ-H2AX, was significantly inhibited following the cyclic stretch exposure. These results indicate that cyclic stretch-induced morphological changes of the nucleus possibly improve the UV radiation resistance in XTC-YF cells, and this improvement may be caused by intracellular force-induced chromatin condensation. To our knowledge, this study is the first to demonstrate the inhibition of UV radiation-induced DNA damage by mechanical stimulation., Japan Soc. of Med. Electronics and Biol. Engineering
Transactions of Japanese Society for Medical and Biological Engineering, 2016, [Reviewed]

〔Major achievements〕細胞の基板接着・伸展過程における焦点接着斑の形態変化の解析
王軍鋒; 杉田修啓; 長山和亮; 松本健郎, Focal adhesions (FAs) play important roles in keeping cell morphology. However, how FAs change during cell adhesion is not clear yet. In this study, we observed change in FA morphology during adhesion process of MC3T3-E1 cells to substrate. We plated the cells whose cycle had been synchronized by serum starvation on glass bottom dishes and cultured for 10 min to 24 h, and stained F-actin, vinculin and nucleus. We measured cell area, aCell, mean area of each FA, aFA, number of FAs per cell, nFA. aCell, aFA, and nFA increased monotonously until 1 h. While aCell continued to increase, aFA and nFA had complex time course that had a downtrend with ups and downs until 12 h and had a simple uptrend afterwards. These might indicate that aFA, and nFA increased in order to strengthen the adhesion of cell to substrate in the early stage of adhesion. We also found that aFA, and nFA of FAs outside the nucleus had a positive correlation to the cell area outside the nucleus until 50 min while nFA of FAs beneath the nucleus had a positive correlation to the area of nucleus after 1 h. This may indicate that the FAs in the two areas have different roles in cell adhesion., 日本生体医工学会
生体医工学, 15 Dec. 2015, [Reviewed]

〔Major achievements〕アクチンストレスファイバーによる細胞の形・構造・力の再現　　　　　　　　　　　　　　　
長山和亮, Lead
科学研究費・新学術領域研究「動く細胞と場のクロストークによる秩序の生成」，2015ニュースレター, 01 Nov. 2015, [Invited]

Nuclear mechanics and mechanotransduction- the role of the nuclear deformability in cell proliferation
Nagayama K; Murakami Y; Hamaji Y; Sato Y; Matsumoto T, Lead, The Japan Society of Mechanical Engineers
Proceedings of the 8th Asian-Pacific Conference on Biomechanics, 16 Sep. 2015, [Reviewed]

〔Major achievements〕Dynamics of actin filaments during adhesion process of MC3T3E-1 cells to substrate
Wang J; Sugita S; Nagayama K; Matsumoto T, In order to determine how cells change their morphology during adhesion process to a substrate, we focused on the actin cytoskeleton and investigated its morphological change along with that of the whole cell during adhesion process. An osteoblastic cell line MC3T3-E1 was used as the test model. We plated cells whose cell cycle had been synchronized by serum starvation on fibronectin-coated glass plate and cultured them for 10 min to 24 h. We then stained their F-actin and nucleus and observed them with a fluorescent microscope for cell area and shape index and 2D parameters for actin morphology, and with a laser scanning microscope for 3D morphology of actin and nucleus. In the beginning of adhesion, the trypsinized cells were round and their nuclei were surrounded uniformly by thick layer of actin. The actin layer in the upper side became actin aggregate (AA) and lower side dense peripheral band (DPB) in 30 min. The upper AA then became smaller and finally to actin filaments (AFs) spanning the cell top. The DPB expanded and finally became AFs on cell bottom by 1 h. The nucleus becomes flattened possibly due to compression by the cell membrane caused by the expansion of the DPB in the early stage of adhesion. In the later stage of adhesion, the number of AFs continuously increased and nucleus became flattened more and more until 12 h. This may be caused by the increase in the top AFs that may compress the nucleus. Cells become more elongated in response to further alignment of AFs until 12 h. These results indicate that change in AFs during adhesion process is complicated not only temporally but also spatially., Japan Society of Mechanical Engineers
Proceedings of the 8th Asian-Pacific Conference on Biomechanics, 16 Sep. 2015, [Reviewed]

Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells
Kazuaki Nagayama; Yumi Hamaji; Yuji Sato; Takeo Matsumoto, The interaction between cells and the extracellular matrix on a topographically patterned surface can result in changes in cell shape and many cellular functions. In the present study, we demonstrated the mechanical deformation and trapping of the intracellular nucleus using polydimethylsiloxane (PDMS)based microfabricated substrates with an array of micropillars. We investigated the differential effects of nuclear deformation on the proliferation of healthy vascular smooth muscle cells (SMCs) and cervical cancer HeLa cells. Both types of cell spread normally in the space between micropillars and completely invaded the extracellular microstructures, including parts of their cytoplasm and their nuclei. We found that the proliferation of SMCs but not HeLa cells was dramatically inhibited by cultivation on the micropillar substrates, even though remarkable deformation of nuclei was observed in both types of cells. Mechanical testing with an atomic force microscope and a detailed image analysis with confocal microscopy revealed that SMC nuclei had a thicker nuclear lamina and greater expression of lamin A/C than those of HeLa cells, which consequently increased the elastic modulus of the SMC nuclei and their nuclear mechanical resistance against extracellular microstructures. These results indicate that the inhibition of cell proliferation resulted from deformation of the mature lamin structures, which might be exposed to higher internal stress during nuclear deformation. This nuclear stress-induced inhibition of cell proliferation occurred rarely in cancer cells with deformable nuclei. (C) 2015 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, Jul. 2015, [Reviewed]

〔Major achievements〕Quantitative analysis of cellular traction forces using a micropillar substrate and estimation of the intracellular force applied to the nucleus
長山和亮, Lead
Transactions of the JSME, 25 Apr. 2015, [Reviewed]

Development of an animal model for flow mediated dilation using rabbit common carotid arteries
YAGUCHI TOSHIYUKI; Kawaguchi Maki; Sugita Shukei; Nagayama Kazuaki; Adachi Eijiro; Matsumoto Takeo, Flow-mediated dilation (FMD) is widely used to diagnose atherosclerosis in its early stage. In FMD, the amount of arterial dilation is assumed to reflect the amount of nitric oxide secreted by endothelial cells (ECs), and thus, healthiness of ECs function. However, the reproducibility of FMD is not enough in some cases, and detailed understanding of these phenomena is necessary. To measure the details of FMD response, we have developed animal FMD model in rabbit common carotid arteries to observe diameter, blood pressure and flow rate directly. We evaluated FMD before and after collapse of the artery. And also, areas of individual ECs and volume of glycocalyx layer on the ECs were measured with a scanning electron microscopy and a fluorescence microscopy , respectively. Collapse of the artery caused significant decrease in FMD (P<0.05), and in the volume of glycocalyx layer per cell (P<0.05), while cell area was increased (P<0.05) possibly because of detachment of some ECs from the intima and its recovery. These results suggest that in situ FMD model we have developed might reproduce FMD response correctly and the decrease of FMD might be caused by decrease of EC function., Japanese Society for Medical and Biological Engineering
Transactions of Japanese Society for Medical and Biological Engineering, 2015

The effects of the mechanical trapping of the nucleus on the cell proliferation using a micropillar substrate
NAGAYAMA KAZUAKI; MURAKAMI YUKI; HAMAJI YUMI; SATO YUJI; MATSUMOTO TAKEO, It has recently been proposed that the cell nucleus acts as a mechanosensor, and the changes in nuclear mechanical environment affect cell functions. However, the physiological roles of the nuclear deformation are unclear at this stage. Here we investigated the effects of nuclear deformation on cellular events, such as cell proliferation, using microfabricated substrates with an array of micropillars. We found that the proliferation of vascular smooth muscle cells (SMCs) but not cervical cancer HeLa cells was dramatically inhibited on the micropillar substrates, even though remarkable nuclear deformation was observed in both types of cells. Mechanical testing with AFM revealed that SMC nuclei were over three times stiffer than those of HeLa, which consequently increased the nuclear mechanical resistance against extracellular microstructures. These results indicate that the proliferation inhibition resulted from deformation of the nucleus, which might be exposed to higher internal stress during nuclear deformation. This nuclear stress-induced inhibition of cell proliferation scarcely occurred in HeLa with deformable nuclei., Japanese Society for Medical and Biological Engineering
Transactions of Japanese Society for Medical and Biological Engineering, 2015

Differences in elastic fiber content and mechanical properties between two types of abdominal aortic aneurysm models of rats
SUGITA SHUKEI; MATSUKAWA SHUN; NAGAYAMA KAZUAKI; MATSUMOTO TAKEO, Various aortic aneurysm models have been developed in animals to simulate human aortic aneurysms. Although all of the models are similar in shape, differences in mechanical properties among models remain unclear. In this study, two aneurysm models were constructed and their mechanical properties and composition of elastic fibers were evaluated. After the abdominal aorta of Wister rat was exposed, elastase (Group E) or both elastase and CaCl₂ (Group EC) were applied to its surface. Incision was then closed and the rat was kept for four weeks. Normal untreated rat was used as control (Group N). After the aorta was excised, the pressure-diameter test and the Elastic Van Gieson stain were performed. Diameter was significantly larger at 80 mmHg and the pressure-strain elastic modulus and area fraction of elastic fibers were significantly lower in Group EC than N, but the difference was insignificant between Group E and N. These results indicate that mechanical properties and tissue composition are different between aneurysm models, and thus a suitable aneurysm model should be selected depending on purposes of studies., Japanese Society for Medical and Biological Engineering
Transactions of Japanese Society for Medical and Biological Engineering, 2015

Analysis of morphological changes in focal adhesion during cell adhesion and spreading on glass substrate
Junfeng Wang; Shukei Sugita; Kazuaki Nagayama; Takeo Matsumoto, When trypsinized cells are seeded on a substrate, the initially spherical cells adhere to the substrate and spread extensively over time. During this process, focal adhesions (FAs), which are large protein complexes organized at the basal surface of cells, physically connect actin filaments to the extracellular matrix and play crucial roles in cellular morphology and signaling. However, the dynamics of substrate adhesion and morphological changes of the spherical cells remain unknown. In this study, we plated MC3T3-E1 osteoblast-like cells, which had been cell cycle-synchronized by serum starvation, to fibronectin-coated glass bottom dishes, and cultured for 10 min to 24 h to observe changes in FA morphology by measuring the cell area (Acell) and FA morphological parameters including mean area of each FA (AFA), number of FAs per cell (NFA), and total area of FAs per cell (TAFA). Subsequently, we investigated the size dependence of FA dynamics. We also analyzed FA density (DFA), size (SFA) and shape index (SIFA) to compare the morphology between FAs that are underneath the nucleus to the morphology of FAs outside the nucleus. We found that Acell, AFA, NFA and TAFA increased continuously until 60 min post-plating. Acell continued to increase after 60 min, while AFA, NFA and TAFA showed complex changes over time. The percentage of small FAs was the highest early during adhesion (20 min) and decreased over time, while the percentage of moderate-to-large FAs increased until 1 h. After 1h, the percentages of small and middle FAs showed little changes, while the percentage of large FAs decreased gradually. These complex changes may reflect cellular demand for FAs. FAs underneath the nuclei were generally smaller than those outside the nuclei during the observed period. The density of FAs increased after 6 h, and FA shape became rounder after 3 h. These differences may be caused by regional differences in FA function: FAs underneath the nucleus may connect the nucleus to the substrate, while those outside the nucleus may connect the whole cell body to the substrate. We confirmed that FAs underwent time-dependent morphological changes during the adhesion process, including changes in size and position., Japan Soc. of Med. Electronics and Biol. Engineering
Transactions of Japanese Society for Medical and Biological Engineering, 2015, [Reviewed]

Multiphasic stress relaxation response of freshly isolated and cultured vascular smooth muscle cells measured by quasi-in situ tensile test
Kazuaki Nagayama; Shunsuke Saito; Takeo Matsumoto, Vascular smooth muscle cells (SMCs) undergo a phenotypic change from a contractile to a synthetic state under pathological conditions, such as atherogenesis and restenosis. Although the viscoelastic properties of SMCs are of particular interest because of their role in the development of these vascular diseases, the effects of phenotypic changes on their viscoelastic properties are unclear at this stage. We performed the stress relaxation test at constant strain (epsilon = 30%) for the freshly isolated contractile SMCs (FSMCs) and the cultured synthetic SMCs (CSMCs) maintaining in situ cell shape and cytoskeletal integrity. We also investigated the effect of extracellular Ca2+ on their viscoelastic behaviors. FSMCs and CSMCs exhibited multiphasic stress relaxation, which consisted of rapid relaxation, occurring on a time scale of several seconds and several 10 seconds, and slow relaxation occurring on a time scale of 1000 seconds. The estimated elastic modulus of CSMCs was less than one-half that of FSMCs, that was associated with a decreased of amount of actin stress fibers (SFs) during the transition from contractile to synthetic phenotypes. FSMCs showed a conservation of tension with extracellular Ca2+ following rapid stress relaxation. In contrast, CSMCs showed a consecutive decrease in tension independent of Ca2+. This suggests that the decrease in tension in a long time scale may be involved in mechanical remodeling of SFs induced through a Rho-dependent pathway, which is Ca2+-independent and become predominant in the transition from contractile to synthetic phenotypes., IOS PRESS
BIO-MEDICAL MATERIALS AND ENGINEERING, 2015, [Reviewed]

Analysis of the Cytoskeleton-Nucleus Mechanotransduction Pathway: Direct Force Transmission from the Actin Stress Fibers to the Nucleus, Proc. of The 4th Japan-Switzerland Workshop on Biomechanics, 16, (2014)　　　　　　　　　　　　　　　
K Nagayama; S Yamazaki; Y Yahiro; T Matsumoto, Lead
Proc. of The 4th Japan-Switzerland Workshop on Biomechanics, 05 Sep. 2014, [Reviewed]

Mechanical interaction between actin stress fibers and the nucleus: Direct force transmission from the whole-cell level to the nucleus　　　　　　　　　　　　　　　
K Nagayama; Y Yahiro; S Yamazaki; T Matsumoto, Lead
Proc. of 7th World Congress of Biomechanics (WBC2014), 07 Jul. 2014, [Reviewed], [Invited]

Changes in the mechanical environment of nucleus during the phenotypic changes of vascular smooth muscle cells　　　　　　　　　　　　　　　
K Nagayama; M Iwata; Y Hamaji; T Matsumoto, Lead
Proc. of International Symposium on Mechanobiology 2014 (ISMB2014), 20 May 2014, [Invited]

Estimation of the mechanical connection between apical stress fibers and the nucleus in vascular smooth muscle cells cultured on a substrate
Kazuaki Nagayama; Sho Yamazaki; Yuki Yahiro; Takeo Matsumoto, Actin stress fibers (SFs) generate intercellular tension and play important roles in cellular mechanotransduction processes and the regulation of various cellular functions. We recently found, in vascular smooth muscle cells (SMCs) cultured on a substrate, that the apical SFs running across the top surface of the nucleus have a mechanical connection with the cell nucleus and that their internal tension is transmitted directly to the nucleus. However, the effects of the connecting conditions and binding forces between SFs and the nucleus on force transmission processes are unclear at this stage. Here, we estimated the mechanical connection between apical SFs and the nucleus in SMCs, taking into account differences in the contractility of individual SFs, using experimental and numerical approaches. First, we classified apical SFs in SMCs according to their morphological characteristics: one subset appeared pressed onto the apical surface of the nucleus (pressed SFs), and the other appeared to be smoothly attached to the nuclear surface (attached SFs). We then dissected these SFs by laser irradiation to release the pretension, observed the dynamic behavior of the dissected SFs and the nucleus, and estimated the pretension of the SFs and the connection strength between the SFs and the nucleus by using a simple viscoelastic model. We found that pressed SFs generated greater contractile force and were more firmly connected to the nuclear surface than were attached SFs. We also observed line-like concentration of the nuclear membrane protein nesprin 1 and perinuclear DNA that was significantly located along the pressed SFs. These results indicate that the internal tension of pressed SFs is transmitted to the nucleus more efficiently than that of attached SFs, and that pressed SFs have significant roles in the regulation of the nuclear morphology and rearrangement of intranuclear DNA. (C) 2014 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, Apr. 2014, [Reviewed]

3P181 Effects of Actin-Nucleus Connections on the Vascular Smooth Muscle Cell Differentiation(Cell biology,Poster,The 52th Annual Meeting of the Biophysical Society of Japan(BSJ2014))
Kazuaki Nagayama; Makoto Iwata; Takeo Matsumoto, The Biophysical Society of Japan General Incorporated Association
Seibutsu Butsuri, 2014

Non-invasive measurement of pressure-diameter relationship and stiffness of human brachial artery through transmural pressure manipulation
Yaguchi Toshiyuki; Nagayama Kazuaki; Tsukahara Hiromasa; Masuda Hiroshi; Matsumoto Takeo, A novel apparatus for in vivo evaluation of arterial mechanical property through transmural pressure (Tp) manipulation was developed. The mechanical properties were measured as pressure-diameter relationship (PDR). A rigid air-tight chamber equipped with an ultrasound probe was attached to the upper arm to manipulate Tp of the brachial artery by changing the pressure in the chamber. The PDR was measured by pressurizing and depressurizing the chamber from 0 mmHg to diastolic pressure and from 0 mmHg to -100 mmHg linearly at the rates of 3, 7, or 10 mmHg/s. PDR obtained at 3 mmHg/s showed active contraction of smooth muscle cells. Loading rate of 10 mmHg/s was too fast to obtain enough data points. Loading rate of 7 mmHg/s was appropriate for PDR measurement. The PDR curves showed nonlinearity typical to arteries., Japanese Society for Medical and Biological Engineering
BME, 2014

On the roles of actin stress fibers on the mechanical regulation of nucleus in adherent cells
K. Nagayama; Y. Yahiro; S. Yamazaki; M. Ukiki; T. Matsumoto, Actin stress fibers (SFs) play important roles in cellular mechanotransduction and regulation of various cellular functions. SFs generate internal tension and contribute to physical interactions between cells and extracellular matrices. It has recently been suggested that cytoskeletons have the potential to interact with the nuclei via nuclear membrane proteins. However, it remains unclear at this stage whether SFs are involved in a mechanical interaction with the nucleus, and their internal forces are transmitted directly to the nucleus and influence the intranuclear DNA. Here we investigated the roles of SFs on the mechanical regulation of the nucleus in vascular smooth muscle cells (SMCs) on a substrate. We microdissected apical stress fibers (ASFs) running across the top surface of nucleus or basal stress fibers (BSFs) underneath the nucleus by using a laboratory- built laser nano-scissor and observed the subsequent mechanical responses of the SFs and the nucleus. Shortening of the dissected fibers was significantly greater in the ASFs than in the BSFs. Nuclei also moved in the direction of retraction of the dissected fibers, and displacement of the nucleus was more remarkable after the dissection of the ASFs than after that of the BSFs. These results indicate that ASFs over the nucleus stabilize the position of the nucleus, and that the internal tension of SFs significantly affects nuclear movement. A line-like concentration of intranuclear DNA along ASFs was often observed near the upper surface of the nucleus. These line-like structures of DNA disappeared and changed markedly following the dissection and shortening of ASFs. Interestingly, the dissected ASFs reorganized near their original location in several tens of minutes following ASF dissection in some cases. Intranuclear DNA also aggregated along the reorganized ASFs and aligned in the direction of the fibers. These dynamic realignments of DNA along the reorganized ASFs may be due to interactions between SFs and perinuclear DNA. This interaction may play a role in the stabilization and positional memory of DNA in the nucleus., Springer Verlag
IFMBE Proceedings, 2014, [Reviewed]

Development of a novel non-invasive measurement method for pressure-diameter relationship of human radial artery and an assessment of their dependence on smooth muscle contraction　　　　　　　　　　　　　　　
Yaguchi T; Takezawa K; Nagayama K; Masuda H; Matsumoto T
Life Support, Dec. 2013, [Reviewed]

Apical and Basal Stress Fibers have Different Roles in Mechanical Regulation of the Nucleus in Smooth Muscle Cells Cultured on a Substrate
Kazuaki Nagayama; Yuki Yahiro; Takeo Matsumoto, Actin stress fibers (SFs) play important roles in cellular mechanotransduction and in regulation of various cellular functions. Stress fibers generate internal tension and contribute to physical interactions between cells and extracellular matrices. We recently found that SFs in vascular smooth muscle cells (SMCs) cultured on a two-dimensional substrate mechanically interact with cell nucleus via nuclear membrane proteins, and that the internal tension of SFs is transmitted directly to the nucleus. However, SFs exist on both the apical side and the basal side of adherent cells on a substrate, and it remains unclear whether these two types of SFs play different roles on the mechanical environment around the nucleus. Here, we investigated differences between the apical and basal stress fibers (BSFs) in SMCs by using a laser nano-scissor technique. We microdissected apical SFs running across the top surface of nucleus (actin cap fibers: ACFs) or BSFs underneath the nucleus by using a laboratory-built laser nano-scissor and observed the subsequent mechanical responses of the SFs and the nucleus. Shortening of the dissected fibers was significantly greater in the ACFs than in the BSFs. Nuclei also moved in the direction of retraction of the dissected fibers, and displacement and local deformation of the nucleus was more remarkable after the dissection of the ACFs than after that of the BSFs. ACFs mostly aligned in the major axis of the nucleus, whereas BSFs showed a weak alignment with asymmetry: the direction of BSFs was rotated clockwise by similar to 10A degrees from the major axis of the nucleus. These results indicate that ACFs and BSFs play different roles in mechanical regulation of the nucleus, and that intracellular tension is transmitted to the nucleus more efficiently by ACFs. ACFs may play significant roles in controlling the intranuclear distribution of DNA through intracellular orientation and positioning of the nucleus., SPRINGER
CELLULAR AND MOLECULAR BIOENGINEERING, Dec. 2013, [Reviewed]

Directional migration of leading-edge mesoderm generates physical forces: Implication in Xenopus notochord formation during gastrulation
Yusuke Hara; Kazuaki Nagayama; Takamasa S. Yamamoto; Takeo Matsumoto; Makoto Suzuki; Naoto Ueno, Gastrulation is a dynamic tissue-remodeling process occurring during early development and fundamental to the later organogenesis. It involves both chemical signals and physical factors. Although much is known about the molecular pathways involved, the roles of physical forces in regulating cellular behavior and tissue remodeling during gastrulation have just begun to be explored. Here, we characterized the force generated by the leading edge mesoderm (LEM) that migrates preceding axial mesoderm (AM), and investigated the contribution of LEM during Xenopus gastrulation. First, we constructed an assay system using micro-needle which could measure physical forces generated by the anterior migration of LEM, and estimated the absolute magnitude of the force to be 20-80 nN. Second, laser ablation experiments showed that LEM could affect the force distribution in the AM (i.e. LEM adds stretch force on axial mesoderm along anterior-posterior axis). Third, migrating LEM was found to be necessary for the proper gastrulation cell movements and the establishment of organized notochord structure; a reduction of LEM migratory activity resulted in the disruption of mediolateral cell orientation and convergence in AM. Finally, we found that LEM migration cooperates with Wnt/PCP to form proper notochord.
These results suggest that the force generated by the directional migration of LEM is transmitted to AM and assists the tissue organization of notochord in vivo independently of the regulation by Wnt/PCP. We propose that the LEM may have a mechanical role in aiding the AM elongation through the rearrangement of force distribution in the dorsal marginal zone. (C) 2013 Elsevier Inc. All rights reserved., ACADEMIC PRESS INC ELSEVIER SCIENCE
DEVELOPMENTAL BIOLOGY, Oct. 2013, [Reviewed]

Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21
Toshihiro Banjo; Janin Grajcarek; Daisuke Yoshino; Hideto Osada; Kota Y. Miyasaka; Yasuyuki S. Kida; Yosuke Ueki; Kazuaki Nagayama; Koichi Kawakami; Takeo Matsumoto; Masaaki Sato; Toshihiko Ogura, Heartbeat is required for normal development of the heart, and perturbation of intracardiac flow leads to morphological defects resembling congenital heart diseases. These observations implicate intracardiac haemodynamics in cardiogenesis, but the signalling cascades connecting physical forces, gene expression and morphogenesis are largely unknown. Here we use a zebrafish model to show that the microRNA, miR-21, is crucial for regulation of heart valve formation. Expression of miR-21 is rapidly switched on and off by blood flow. Vasoconstriction and increasing shear stress induce ectopic expression of miR-21 in the head vasculature and heart. Flow-dependent expression of mir-21 governs valvulogenesis by regulating the expression of the same targets as mouse/human miR-21 (sprouty, pdcd4, ptenb) and induces cell proliferation in the valve-forming endocardium at constrictions in the heart tube where shear stress is highest. We conclude that miR-21 is a central component of a flow-controlled mechanotransduction system in a physicogenetic regulatory loop., NATURE PUBLISHING GROUP
NATURE COMMUNICATIONS, Jun. 2013, [Reviewed]

〔Major achievements〕Low-flow-resistance Methacrylate-based Polymer Monolithic Column Prepared by Low-conversion Ultraviolet Photopolymerization at Low Temperature
Tomohiko Hirano; Ayumi Kobayashi; Takuya Nakaza; Shinya Kitagawa; Hajime Ohtani; Kazuaki Nagayama; Takeo Matsumoto, A low-conversion poly(butyl methacrylate-co-ethylene dimethacrylate)-based polymer monolithic column was prepared by ultraviolet (UV) irradiation for a short time at a low temperature (-15 degrees C). By UV irradiation for 2 min, the monolithic column exhibited a high permeability of 5.6 x 10(-13) m(2) and a high column efficiency of over 100000 plates m(-1). At this polymerization time, the conversions of butyl methacrylate and ethylene dimethacrylate were only 10 and 21%, respectively, as determined by pyrolysis gas chromatography. The low conversion led to high porosity, which in turn resulted in high permeability. The reduction in conversion also contributed to improve the compositional homogeneity of the prepared polymer monolith, which would promote high column efficiency. Using the prepared low-conversion column in conjunction with a vacuum-driven low-pressure HPLC without a conventional high-pressure pump, the separation of alkylbenzenes was successfully achieved using a low pressure of only -0.045 MPa to generate the mobile phase stream., JAPAN SOC ANALYTICAL CHEMISTRY
Analytical Sciences, Feb. 2013, [Reviewed]

1P190 Actin cap fibers and basal stress fibers have different roles in mechanical regulation of nucleus in vascular smooth muscle cells(12.Cell biology,Poster,The 51st Annual Meeting of the Biophysical Society of Japan)
Nagayama Kazuaki; Yahiro Yuki; Ukiki Mitsuhiro; Matsumoto Takeo, The Biophysical Society of Japan General Incorporated Association
Seibutsu Butsuri, 2013

Development of a Non-invasive Multifaceted Evaluation System for Arterial Function under Transmural Pressure Manipulation
Toshiyuki Yaguchi; Kazuaki Nagayama; Hiromasa Tsukahara; Hiroshi Masuda; Takeo Matsumoto, A novel apparatus for multifaceted evaluation of arterial function was developed in which functions of endothelial cells and smooth muscle cells and the function of the artery as a conduit tube, i.e., mechanical properties were measured. A rigid airtight chamber with an ultrasound probe was attached to the upper arm to manipulate transmural pressure (TP) of the brachial artery by changing the pressure in the chamber. Pressure-diameter curve of the artery was obtained by measuring the diameter change with the probe during TP manipulation. Endothelial function was measured with a standard FMD (flow-mediated dilation) protocol. Smooth muscle function was evaluated with its myogenic response, pressure-mediated contraction (PMC), i.e., spontaneous contraction of the artery following its stepwise passive dilation caused by the stepwise application of negative pressure to the chamber. Examples of pressure-diameter curves, FMD and PMC results are presented. Pressure-diameter relationship of the brachial artery could be obtained reproducibly over a wide range of TP. Contrary to intuition, the diameter decreased and increased when TP increased and decreased, respectively, in some TP ranges. PMC and FMD measurements showed reasonable results with active contraction and dilation of smooth muscle cells, respectively. This apparatus may be useful to measure not only pressure-diameter relationship but also contractility of smooth muscle cell., IEEE
2013 INTERNATIONAL SYMPOSIUM ON MICRO-NANOMECHATRONICS AND HUMAN SCIENCE (MHS), 2013, [Reviewed]

Laser Nano-Dissection for Analysis of Cellular Mechanotransduction: Direct Force Transmission from Actin Stress Fibers to Nucleus: Tensional Homeostasis of Vascular Smooth Muscle Cells　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; Akifumi ADACHI; Keisuke SASASHIMA; and Takeo MATSUMOTO, Lead
Proceedings of the 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, 2013, [Reviewed]

Heterogeneity in Microscopic Residual Stress in the Aortic Wall
Takeo MATSUMOTO; Akihisa FUKUNAGA; Kengo NARITA; Yohei UNO; Kazuaki NAGAYAMA, Last, Aortic wall has a concentric layered structure which is a pair of relatively stiff elastic lamina (EL) and a relatively soft smooth muscle cell (SMC)-rich layer. If soft and stiff layers bear the same stress in a loaded state, tensile and compressive residual stress should appear in the soft and stiff layer, respectively, in an unloaded state. In fact, ELs are corrugated and SMCs remain stretched in an unloaded aortic wall, and ELs become straight and SMCs shrink upon isolation from the surrounding tissues. As an index of compressive residual stress, a waviness W, defined as the length along its corrugation divided by its straight length, was calculated in the sections of porcine thoracic aortas. The waviness varied widely, ranging from 1.00 to 1.35. The variation of the waviness caused wide variation of the stress borne by the ELs. For example, estimated stress was as high as 150kPa for the ELs with W = 1.00, and was 0 kPa for the ELs with W = 1.35. The reason for the large difference in the stress in the ELs is unclear at this stage. This may be caused by local activities of the smooth muscle cells such as wall remodeling and cell division. © The Society for Experimental Mechanics, Inc. 2014.
Proceedings of 2013 SEM Annual Conference & Exposition on Experimental & Applied Mechanics, 2013, [Reviewed]

On the roles of actin stress fibers on the mechanical environment of nucleus in vascular smooth muscle cells　　　　　　　　　　　　　　　
Kazuaki Nagayama; Yuki Yahiro; Takeo Matsumoto
Recent Advances in Mechanobiology (Shi Y, Sokabe M, Kung C, Martinac B, Naruse K, Dzwolak W, eds), Nov. 2012

Strain waveform dependence of stress fiber reorientation in cyclically stretched osteoblastic cells: effects of viscoelastic compression of stress fibers
Kazuaki Nagayama; Yuki Kimura; Narutaka Makino; Takeo Matsumoto, Nagayama K, Kimura Y, Makino N, Matsumoto T. Strain waveform dependence of stress fiber reorientation in cyclically stretched osteoblastic cells: effects of viscoelastic compression of stress fibers. Am J Physiol Cell Physiol 302: C1469-C1478, 2012. First published February 22, 2012; doi:10.1152/ajpcell.00155.2011.-Actin stress fibers (SFs) of cells cultured on cyclically stretched substrate tend to reorient in the direction in which a normal strain of substrate becomes zero. However, little is known about the mechanism of this reorientation. Here we investigated the effects of cyclic stretch waveform on SF reorientation in osteoblastic cells. Cells adhering to silicone membranes were subjected to cyclic uniaxial stretch, having one of the following waveforms with an amplitude of 8% for 24 h: triangular, trapezoid, bottom hold, or peak hold. SF reorientation of these cells was then analyzed. No preferential orientation was observed for the triangular and the peak-hold waveforms, whereas SFs aligned mostly in the direction with zero normal strain (similar to 55 degrees) with other waveforms, especially the trapezoid waveform, which had a hold time both at loaded and unloaded states. Viscoelastic properties of SFs were estimated in a quasi-in situ stress relaxation test using intact and SF-disrupted cells that maintained their shape on the substrate. The dynamics of tension F-SFs acting on SFs during cyclic stretching were simulated using these properties. The simulation demonstrated that F-SFs decreased gradually during cyclic stretching and exhibited a compressive value (F-SFs < 0). The magnitude and duration time of the compressive forces were relatively larger in the group with a trapezoid waveform. The frequency of SF orientation had a significant negative correlation with the applied compressive forces integrated with time in a strain cycle, and the integrated value was largest with the trapezoid waveform. These results may indicate that the applied compressive forces on SFs have a significant effect on the stretch-induced reorientation of SFs, and that SFs realigned to avoid their compression. Stress relaxation of SFs might be facilitated during the holding period in the trapezoid waveform, and depolymerization and reorientation of SFs were significantly accelerated by their viscoelastic compression., AMER PHYSIOLOGICAL SOC
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, May 2012, [Reviewed]

〔Major achievements〕Dynamic Changes of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate: Tensional homeostasis of aortic smooth muscle cells
Nagayama K; Adachi A; Matsumoto T, Lead, In order to determine how cells change their traction forces at focal adhesions (FAs) under macroscopic deformation conditions, we investigated the dynamic changes in traction force at FAs by culturing porcine aortic smooth muscle cells (SMCs) on elastic micropillar substrates and giving them macroscopic deformation by stretching the substrates. We patterned adhesion region on the top surface of a polydimethylsiloxane-based micropillar array using our original micropatterning technique to align the cells on the pillar array parallel to the stretch direction. SMCs plated on the micropillars successfully spread in the adhesion region and their actin stress fibers (SFs) aligned in the direction to be stretched. Cells were then stretched and released cyclically with strain rates of 0.3%/15s up to 3-6% strain, and deflection of micropillars at both side regions of cells were measured simultaneously to obtain the traction force at each FA in situ. SMCs aligned in the stretch direction showed two types of responses: almost a half of the SMCs changed their force in phase with the applied strain, and showed gradual active contraction with the stretch cycles (synchronous group)
and the rest tended to keep their force constant and became elongated with the cycles (asynchronous group). In the asynchronous group, the force sometimes changed in antiphase with the cell strain as if the cells maintain intracellular traction force at a constant level. These results may indicate that SMCs sometimes exhibit active homeostatic responses to keep their pretension constant during macroscopic stretching, and such tensional homeostatic responses may occur concurrently with cell elongation. © 2012 by JSME.
Journal of Biomechanical Science and Engineering, Mar. 2012, [Reviewed]

Tensile properties of vascular smooth muscle cells: Bridging vascular and cellular biomechanics
Takeo Matsumoto; Kazuaki Nagayama, Vascular walls change their dimensions and mechanical properties adaptively in response to blood pressure. Because these responses are driven by the smooth muscle cells (SMCs) in the media, a detailed understanding of the mechanical environment of the SMCs should reveal the mechanism of the adaptation. As the mechanical properties of the media are highly heterogeneous at the microscopic level, the mechanical properties of the cells should be measured directly. The tensile properties of SMCs are, thus, important to reveal the microscopic mechanical environment in vascular tissues; their tensile properties have a close correlation with the distribution and arrangement of elements of the cytoskeletal networks, such as stress fibers and microtubules. In this review, we first introduce the experimental techniques used for tensile testing and discuss the various factors affecting the tensile properties of vascular SMCs. Cytoskeletal networks are particularly important for the mechanical properties of a cell and its mechanism of mechanotransduction; thus, the mechanical properties of cytoskeletal filaments and their effects on whole-cell mechanical properties are discussed with special attention to the balance of intracellular forces among the intracellular components that determines the force applied to each element of the cytoskeletal filaments, which is the key to revealing the mechanotransduction events regulating mechanical adaptation. Lastly, we suggest future directions to connect tissue and cell mechanics and to elucidate the mechanism of mechanical adaptation, one of the key issues of cardiovascular solid biomechanics. (C) 2011 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, Mar. 2012, [Reviewed], [Invited]

In-Situ Measurement of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; Yuki Yahiro; and Takeo MATSUMOTO, Lead
Proceedings of the Ninth International Conference on Flow Dynamics, 2012, [Reviewed]

Development of a Novel Magnetic-Driven Micropillar Substrate for Mechanical Stimulation at Individual Focal Adhesions of Cells
Kazuaki NAGAYAMA; Yasuhiro HAMADA; Takuya INOUE; and Takeo MATSUMOTO, Lead, AMER SOC MECHANICAL ENGINEERS
Proceedings of the 2012 Summer Bioengineering Conference, 2012, [Reviewed]

Stress fibers stabilize the position of intranuclear DNA through mechanical connection with the nucleus in vascular smooth muscle cells
Kazuaki Nagayama; Yuki Yahiro; Takeo Matsumoto, Actin stress fibers (SFs) running across the top surface of the nucleus in vascular smooth muscle cells were dissected using laser nano-dissection technique to release its pretension, and the dynamic behavior of SFs, nucleus, and intranuclear DNA were investigated. SFs shortened across the top surface of the nuclei after their dissection. The nuclei moved in the direction of SF retraction, and showed marked local deformation, indicating that SFs firmly connected to the nuclear surface. Intranuclear DNA located near and around the dissected SFs disappeared and their distribution changed markedly. These findings suggest that SFs stabilize the position of intranuclear chromatin through mechanical connection with the nucleus. The tension of SFs may be transmitted mechanically to the nucleus inducing conformational changes of intranuclear chromatin. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved., WILEY
FEBS LETTERS, Dec. 2011, [Reviewed]

Heterogeneous response of traction force at focal adhesions of vascular smooth muscle cells subjected to macroscopic stretch on a micropillar substrate
Kazuaki Nagayama; Akifumi Adachi; Takeo Matsumoto, Traction force generated at focal adhesions (FAs) of cells plays an essential role in regulating cellular functions. However, little is known about how the traction force at each FA changes during cell stretching. Here we investigated dynamic changes in traction force at FAs during macroscopic stretching of porcine aortic smooth muscle cells (SMCs) cultured on elastic micropillar substrates. SMCs were cultured on polydimethylsiloxane (PDMS)-based substrates with a micropillar array, and stretched approximately in the direction of their major axis and then released by stretching and relaxing the substrates. This stretch-release cycle was repeated twice with cell strain rates of 0.3%/15 s up to a 3% strain, and the deflection of the PDMS micropillars was measured simultaneously to obtain the traction force at each FA F, total force in the cell's major axis direction F(all), and whole-cell strain epsilon(cell). Traction forces of SMCs during stretching varied widely with location: their changes at some pillars synchronized well with the applied strain epsilon(cell), but others did not synchronized. Whole-cell stiffness estimated as the slope of the loading limb of the F(all)-epsilon(cell) curves was similar to 10 nN/%, which was the same order of magnitude of the reported stiffness of cultured SMCs obtained in a tensile test. Interestingly, F(all) at a zero-strain state (pretension at the whole-cell level) actively increased in some cells following the loading/unloading process, as did whole-cell stiffness. Such a change did not occur in cultured SMCs in the tensile test in which cells were held with a pair of micropipettes coated with nonspecific adhesive. These results indicate that SMCs showed a myogenic response when stretched through their multiple FAs, but not through nonspecific adhesions on their membrane. SMCs may behave differently depending on the sites through which they are stretched. (C) 2011 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, Oct. 2011, [Reviewed]

Dynamic Change in Morphology and Traction Forces at Focal Adhesions in Cultured Vascular Smooth Muscle Cells During Contraction
Kazuaki Nagayama; Takeo Matsumoto, In order to study how cells change their traction forces at focal adhesions (FAs) following cell contraction, we observed the dynamic changes in traction forces at FAs, the morphology of FAs, and actin stress fibers (SFs) anchoring FAs in cultured porcine aortic smooth muscle cells (SMCs) during cell contraction. SMCs were cultured on polydimethylsiloxane-based elastic micropillar array substrates, and their traction forces at individual FAs were measured by the deflection of the pillars during cell contraction induced with 10(-4) M serotonin. The traction forces started to increase immediately after the administration of serotonin, especially at the cell periphery, and their direction converged gradually to that of the cell major axis. The directional change of force reached a plateau in the early stages of the contraction. The time constants were significantly smaller for changes in direction (mean +/- standard deviation: 8.0 +/- 4.5 min; 116 pillars of 10 cells) compared to those concerning the magnitude of the force (16.6 +/- 6.0 min). Surface reflective interference contrast microscopy revealed that the morphological changes in FAs showed a trend similar to that of their forces: FAs grew and aligned in the direction of the cell major axis in the early stage of the contraction. Some FAs then merged and continuously elongated along SFs. The number of FAs and SFs in each cell decreased similarly by 15-20% 60 min after the administration of serotonin, suggesting that contractile activation induced fusion of FAs and of SFs. Total FA area per cell more than doubled in 60 min. These results indicate that FAs may remodel themselves actively during cell contraction depending on the direction and strength of contractile forces of SFs. The fusion of FAs and of SFs may have the directions of the traction forces more coherent, and thus increase the net contraction force generated by each SMC. The concomitant increase in the FA area may make adhesion sites strong enough to transmit the increased force to the extracellular matrix., SPRINGER
CELLULAR AND MOLECULAR BIOENGINEERING, Sep. 2011, [Reviewed]

3K1446 Dynamic behavior of nucleus and intranuclear DNA induced with laser nano-dissection of stress fibers in vascular smooth muscle cells(Cell biology 4,The 49th Annual Meeting of the Biophysical Society of Japan)
Nagayama Kazuaki; Yahiro Yuki; Matsumoto Takeo, The Biophysical Society of Japan General Incorporated Association
Seibutsu Butsuri, 2011

2SQ-05 Artery function evaluation using mechanical responses of cells : early diagnosis of atherosclerosis(2SQ Developing Mechanobiology:from fundamentals to medical applications,The 49th Annual Meeting of the Biophysical Society of Japan)
Matsumoto Takeo; Kurokawa Takahiro; Kato Yoshihito; Nagayama Kazuaki; Tsukahara Hiromasa; Masuda Hiroshi, The Biophysical Society of Japan General Incorporated Association
Seibutsu Butsuri, 2011

Heartbeat regulates cardiogenesis by suppressing retinoic acid signaling via expression of miR-143
Kota Y. Miyasaka; Yasuyuki S. Kida; Toshihiro Banjo; Yosuke Ueki; Kazuaki Nagayama; Takeo Matsumoto; Masaaki Sato; Toshihiko Ogura, Cardiogenesis proceeds with concomitant changes in hemodynamics to accommodate the circulatory demands of developing organs and tissues. In adults, circulatory adaptation is critical for the homeostatic regulation of blood circulation. In these hemodynamics-dependent processes of morphogenesis and adaptation, a mechanotransduction pathway, which converts mechanical stimuli into biological outputs, plays an essential role, although its molecular nature is largely unknown. Here, we report that expression of zebrafish miR-143 is dependent on heartbeat. Knocking-down miR-143 results in de-repression of retinoic acid signaling, and produces abnormalities in the outflow tracts and ventricles. Our data uncover a novel epigenetic link between heartbeat and cardiac development, with miR-143 as an essential component of the mechanotransduction cascade. (C) 2010 Elsevier Ireland Ltd. All rights reserved., ELSEVIER SCIENCE BV
MECHANISMS OF DEVELOPMENT, Jan. 2011, [Reviewed]

In situ observation of nuclear behavior during laser nano-dissection of actin stress fibers: mechanical interaction between actin stress fibers and nucleus
Kazuaki NAGAYAMA; Yuki YAHIRO; and Takeo MATSUMOTO, Lead
Proceedings of the 2011 Summer Bioengineering Conference, 2011, [Reviewed]

How do cells sense substrate stiffness? Effects of substrate elasticity and thickness on the behavior of rat aortic smooth muscle cells
Takeo MATSUMOTO; Noriyuki MATSUI; Mai ISHIGURO; and Kazuaki NAGAYAMA
Proceedings of the 2011 Summer Bioengineering Conference, 2011, [Reviewed]

〔Major achievements〕Mechanics of wrinkle formation: Micromechanical analysis of skin deformation during wrinkle formation in UV-irradiated mice
Matsumoto T; Ikuta N; Mori M; Nagayama K, Lead, Background/purpose
The mechanical aspects of wrinkle formation were studied in the dorsal skin of hairless mice.
Methods
Wrinkles were induced by irradiating with ultraviolet (UV) B for 10 weeks, while observing skin deformation during wrinkle formation. Changes in skin dimensions were also observed during the specimen excision process. Wrinkle depth and interval were measured before and after removal of the cutaneous muscle layer. Local deformation of wrinkled skin during uniaxial stretch was also measured. Changes in curvature of skin specimens upon muscle layer removal were then observed to determine the force balance in skin layers.
Results
The skin showed spontaneous contraction in response to UV irradiation. Wrinkled skin showed a marked decrease in the wrinkle depth and a slight increase in wrinkle interval following muscle layer removal, a peculiar mechanical response that cannot be explained by homogeneous deformation of the skin. This response was due to compressive deformations of dermal tissue caused by the muscle layer and concentrated at valleys of the wrinkles. Curvature measurements indicated that the muscle layer compressed the dermal tissue predominantly in the craniocaudal direction. Morphological observations showed that the wrinkles coincided with rows of pores and sulci cutis, where the structural stiffness of the horny layer was relatively low. The horny layer showed significant thickening.
Conclusion
Taken together, we propose the following hypothetical mechanisms of wrinkle formation during UV irradiation: spontaneous contraction of the dermis while maintaining or increasing the epidermal area induces buckling of the epidermis into the dermis at mechanically weak lines, namely, the rows of pores and sulci cutis, and buckling may be amplified by the axial compression of the dermis by the muscle layer., WILEY-BLACKWELL
Skin Research and Technology, 02 May 2010, [Reviewed]

Estimation of single stress fiber stiffness in cultured aortic smooth muscle cells under relaxed and contracted states: Its relation to dynamic rearrangement of stress fibers
Kazuaki Nagayama; Takeo Matsumoto, For a quantitative analysis of intracellular mechanotransduction, it is crucial to know the mechanical properties of actin stress fibers in situ. Here we measured tensile properties of cultured aortic smooth muscle cells (SMCs) in a quasi-in situ tensile test in relaxed and activated states to estimate stiffness of their single stress fibers (SFs). An SMC cultured on substrates was held using a pair of micropipettes and detached from the substrate while maintaining its in situ cell shape and cytoskeletal integrity. Stretching up to similar to 15% followed by unloading was repeated three times to stabilize their tension-strain curves in the untreated (relaxed) and 10 mu M-serotonin-treated (activated) condition. Cell stiffness defined as the average slope of the loading limb of the stable loops was similar to 25 and similar to 40 nN/% in relaxed and activated states, respectively. It decreased to similar to 10 nN/% following SF disruption with cytochalasin D in both states. The number of SFs in each cell measured with confocal microscopy decreased significantly upon serotonin activation from 21.5 +/- 3.8 (mean +/- SD, n=80) to 17.5 +/- 3.9 (n=77). The dynamics of focal adhesions (FAs) were observed in adherent cells using surface reflective interference contrast microscopy. FAs aligned and elongated along the cell major axis following activation and then merged with each other, suggesting that the decrease in SFs was caused by their fusion. Average stiffness of single SFs estimated by the average decrease in whole-cell stiffness following SF disruption divided by the average number of SFs in each cell was similar to 0.7 and similar to 1.6 nN/% in the relaxed and activated states, respectively. Stiffening of single SFs following SF activation was remarkably higher than stiffening at the whole-cell level. Results indicate that SFs stiffen not only due to activation of the actomyosin interaction, but also due to their fusion, a finding which would not be obtained from analysis of isolated SFs. (C) 2010 Elsevier Ltd. All rights reserved,, ELSEVIER SCI LTD
JOURNAL OF BIOMECHANICS, May 2010, [Reviewed]

T0201-3-6 Observation of microscopic deformation in the porcine thoracic aortic wall during circumferential stretch
UNO Yohei; NAGAYAMA Kazuaki; MATSUMOTO Takeo, The artery walls consist of structural components that have various mechanical properties: elastin, collagen and smooth muscle cells. Such variety may cause heterogeneous deformation of the components at a microscopic level when arterial tissue is subjected to macroscopic uniform stretch. To examine this hypothesis, we sliced 15-μm-thick specimens from porcine thoracic aorta with cryotome, and stretched them under a transmitted light microscope to observe their microscopic deformation caused by macroscopic stretch. Microscopic strain was found to be highly heterogeneous: stretch ratio in the elastic lamina (EL) and smooth muscle layer (SML) was 1.1-2.3 and 1.1-2.1, respectively, at circumferential stretch ratio of 1.5. Strain difference between an EL and a SML adjacent to each other could be as high as 6 times. These results suggest that the microscopic deformation in the artery wall is highly heterogeneous. Mechanical environment of the artery wall might not be so homogeneous at a cellular level., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2010

T0201-2-2 In-situ measurement of traction force at focal adhesions during macroscopic stretch/release of vascular smooth muscle cells
NAGAYAMA Kazuaki; ADACHI Akifumi; MATSUMOTO Takeo, Traction force generated at focal adhesions (FAs) of cells plays an essential role in regulating cellular functions. However, little is known about how the traction force at each FA changes during cell stretching. Here we investigated the changes in traction force at FAs during macroscopic stretching of porcine aortic smooth muscle cells (SMCs) cultured on elastic micropillar substrates. SMCs were plated on a polydimethylsiloxane-based micropillar array substrate. After cell spreading, the SMCs were stretched and released in their major axis direction. These stretch/release cycles were carried out with the strain rates of 0.3%/15s, and the deflection of the micropillars were measured simultaneously to obtain the traction force at each FA. Traction forces at both ends of the cells did not change significantly during the cycles with 3% strain, while the forces changed notably with 6% strain. Interestingly, these forces decreased with increase of their strain and vice versa. These results indicate that the SMCs showed active responses to keep their internal tension constant during the macroscopic stretch/release, namely, mechanical homeostatic responses. SMCs may have a strain threshold to activate these responses., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2010

J0207-1-5 Observation of cell behavior on substrates with elasticity gradient
Nakagawa Takashi; Nagayama Kazuaki; Matsumoto Takeo, To study cell response to substrate stiffness, we observed shape and migration of UV♀2 cells on polyacrylamide gel substrates with elasticity gradient. The substrates were fabricated with a photopolymerization method and had a soft (E=10 kPa) and a stiff (55 kPa) region connected with a transition region with elasticity gradient of ca. 100 kPa/mm. Cells on the stiff region showed an elongated shape and migrated actively, while those on the soft region were round and seldom migrate. On the transition region, cells tended to migrate toward the stiff region. Cells elongate and attach their pseudopod to substrate when they spread and migrate. The connection between pseudopod and substrate might be too weak on soft substrates to withstand intracellular tension developed during cell spreading and migration. We confirmed that difference of substrate stiffness affects cell behavior., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2010

〔Major achievements〕Effects of three-dimensional culture and cyclic stretch stimulation on expression of contractile proteins in freshly isolated rat aortic smooth muscle cells
Nagayama K; Morishima N; Matsumoto T, Lead, The effects of three-dimensional (3-D) culture and cyclic stretch stimulation on the expression of contractile proteins were investigated in freshly isolated rat aortic smooth muscle cells (FSMC). Primary cells were cultured statically on cell culture dishes (two-dimensional (2-D) culture) or in type I collagen gel matrix (3-D culture). Changes in their expression level of actin filaments (AFs) and smooth muscle myosin heavy chain (SM-MHC) were measured quantitatively using an accurately-calibrated fluorescent microscopy. The expression of AFs and SM-MHC decreased in both cultures in their early stages. Cell morphology was quite different between the two cultures: the cells had a flattened and irregular shape in the 2-D culture, while they had a fusiform shape with a well-defined long axis in the 3-D. Nineteen-day culture in the gel significantly increased the expression levels of AFs and SM-MHC while the expression levels remained low in the 2-D. Further and early increase in the expression levels was observed in the cells cultured in the gel with cyclic stretch of ∼8% amplitude and 1 Hz frequency. The cyclic stretch also induced alignment of FSMCs in the gel parallel to the stretch direction, and the cell alignment was observed earlier than the increase in their contractile proteins. These results indicate that the 3-D culture in collagen gel may increase the expression level of contractile proteins in FSMCs while maintaining their fusiform morphology, and cyclic stretch may efficiently increase the expression levels when the cells aligned in the stretch direction., The Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 02 May 2009, [Reviewed]

S0201-3-6 Change in morphology and traction forces at focal adhesions of vascular smooth muscle cells during their contraction
NAGAYAMA Kazuaki; YAHIRO Yuki; MATSUMOTO Takeo, In order to study how intracellular forces are transmitted to the extracellular matrix during cell contraction, we investigated the change in traction forces at focal adhesions (FAs) and morphological changes of FAs in porcine aortic smooth muscle cells (SMCs) during their contraction. SMCs were cultured on polydimethylsiloxane-based micropillar array substrates, and then the traction forces at individual FAs were measured during cell contraction induced with 10^<-4>M serotonin. The traction forces immediately increased after the administration of serotonin especially at cell periphery, and their direction converged gradually to the direction parallel to the cell major axis. Fluctuation of forces was observed at some pillars during cell contraction. Surface reflective interference contrast microscopy revealed that FAs increased their area during cell contraction, and aligned in a direction parallel to the cell major axis. These results suggest that FAs remodel themselves actively during smooth muscle contraction depending on the direction and strength of contractile forces., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2009

S0201-3-4 Research on the sensing mechanism of substrate elasticity by cells : Effects of substrate elasticity and thickness on the behaviour of vascular smooth muscle cells
MATSUI Norihiro; ISHIGURO Mai; NAGAYAMA Kazuaki; MATSUMOTO Takeo, To study sensing mechanism of substrate stiffness by cells, we observed changes of projected area of rat aortic smooth muscle cells (RASMs) cultured on polyacrylamide gel substrates having various elastic moduli E and thicknesses h. Cell area decreased when h increased, and reached plateau when h>7.5 μm for a hard gel (E=92 kPa) and h>30 μm for a soft gel (E=6 kPa). We then performed numerical analysis to know the relationship between displacement of focal adhesions (FAs) and gel thickness, and found that stiffness at FA level correlates well with the cell area. These results suggest that RASMs were able to sense the elastic properties of the substrate only in a shallow region. If the cells sensed mechanical properties of the substrate by force-deformation relation spanning whole cell length, then the sensing depth should be comparable to their dimensions. Cells may sense substrate elasticity not with deformation of whole cell body but with local deformation at FAs., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2009

Intracellular Memory of Stress Fiber Orientation: Focal Adhesions Store It and Microtubules Erase It During Disassembly Reassembly Process of Stress Fibers
Yunfeng YANG; Kazuaki NAGAYAMA; and Takeo MATSUMOTO, Stress fibers (SFs) play essential roles in various cellular functions, and they reorganized in response to changes in mechanical environment. Recently, we noticed that the SF networks reappeared following their temporal disruption with cytochalasin D looked similar to those before disruption in rat aortic smooth muscle cells (SMCs). This indicates that the cells may have a memory of SF orientation. The aim of this study was to clarify the mechanism of the memory focusing on the effects of microtubules (MTs) and focal adhesions (FAs) during the reorganization process of SFs. Firstly, we preconditioned the cells with cyclic stretch to make their SFs align in a uniform direction. After cyclic stretching, we depolymerized SFs completely with cytochalasin D, and let them repolymerize in the drug-free medium. To investigate the effects of MTs during the SF repolymerization, we depolymerized MTs. FAs were observed with a surface reflective interference contrast microscopy. In the presence of MTs, repolymerized SFs were randomly orientated with newly formed FAs. In contrast, in the absence of MTs, FAs were not destroyed and the SF alignment was conserved. These indicate that FAs might store the memory of SF alignment while MTs may erase it., SPRINGER
Proceedings of the World Congress 2009 on Medical Physics and Biomedical Engineering, 2009, [Reviewed]

Effects of cyclic stretch waveform and cell density on the cyclic stretch-induced stress fiber reorientation in osteoblast-like cells　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; Yuki KIMURA; and Takeo MATSUMOTO, Lead
Proceedings of the 4th Asian-Pacific Conference on Biomechanics, 2009, [Reviewed]

Microscopic heterogeneity in the mechanical environment of porcine thoracic aorta　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Akira FUKUNAGA; Kengo NARITA; Takahiro SHIRONO; and Kazuaki NAGAYAMA, Last
Proceedings of the 4th Asian-Pacific Conference on Biomechanics, 2009

Effects of Mechanical Stimulation on the Mechanical Properties and Calcification Process of Immature Chick Bone Tissue in Culture
Takeo MATSUMOTO; Katsuhisa ICHIKAWA; Mashashi NAKAGAKI; and Kazuaki NAGAYAMA, Last, In order to study the adaptation mechanism of bone tissues, we cultured immature bone slices obtained from chick tibia under mechanical stimulation. We first cultured 2 to 3-mm-thick slices for 3 days while giving them cyclic compression up to 0.3N at the rate of 3-4 cycle/min. Both the stiffness and the calcified area of the bone tissues increased significantly under cyclic compression. Such increases did not occur in their static control, nor specimens deactivated with liquid nitrogen. We then cultured 0.2mm-thick slices for 24 hours while being stretched by 10%. Calcified area was significantly larger in stretched specimens than in the non-stretched control. Traveling direction of the calcification was roughly equal to the stretch direction. Collagen fibers showed alignment in the stretch direction over 5% of stretch. These results indicate that dynamic and quasi-static stretch stimulate calcification especially in the direction of stretch, and the calcification may occur preferentially along the direction of collagen fibers. The alignment of collagen fibers in the stretch direction and facilitated calcification along collagen fibers may have something to do with the alignment of trabecular bone in the direction of principal stress., SPRINGER
Proceedings of the 13th International Conference on Biomedical Engineering, 2009

Contribution of actin filaments and microtubules to quasi-in situ tensile properties and internal force balance of cultured smooth muscle cells on a substrate
Kazuaki Nagayama; Takeo Matsumoto, Nagayama K, Matsumoto T. Contribution of actin filaments and microtubules to quasi-in situ tensile properties and internal force balance of cultured smooth muscle cells on a substrate. Am J Physiol Cell Physiol 295: C1569-C1578, 2008. First published October 15, 2008; doi:10.1152/ajpcell.00098.2008.-The effects of actin filaments (AFs) and microtubules (MTs) on quasi-in situ tensile properties and intracellular force balance were studied in cultured rat aortic smooth muscle cells (SMCs). A SMC cultured on substrates was held using a pair of micropipettes, gradually detached from the substrate while maintaining in situ cell shape and cytoskeletal integrity, and then stretched up to similar to 15% and unloaded three times at the rate of 1 mu m every 5 s. Cell stiffness was similar to 20 nN per percent strain in the untreated case and decreased by similar to 65% and similar to 30% following AF and MT disruption, respectively. MT augmentation did not affect cell stiffness significantly. The roles of AFs and MTs in resisting cell stretching and shortening were assessed using the area retraction of the cell upon noninvasive detachment from thermoresponsive gelatin-coated dishes. The retraction was similar to 40% in untreated cells, while in AF-disrupted cells it was <20%. The retraction increased by similar to 50% and decreased by similar to 30% following MT disruption and augmentation, respectively, suggesting that MTs resist intercellular tension generated by AFs. Three-dimensional measurements of cell morphology using confocal microscopy revealed that the cell volume remained unchanged following drug treatment. A concomitant increase in cell height and decrease in cell area was observed following AF disruption and MT augmentation. In contrast, MT disruption significantly reduced the cell height. These results indicate that both AFs and MTs play crucial roles in maintaining whole cell mechanical properties of SMCs, and that while AFs act as an internal tension generator, MTs act as a tension reducer, and these contribute to intracellular force balance three dimensionally., AMER PHYSIOLOGICAL SOC
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, Dec. 2008, [Reviewed]

529 Study on the Reproducibility of Stress Fiber Orientation in Aortic Smooth Muscle Cells : Effects of Microtubules and Focal Adhesions
YANG Yunfeng; NAGAYAMA Kazuaki; MATSUMOTO Takeo, Stress fibers (SFs) play essential roles in various cellular functions such as cell movement, shape maintenance and cell division. In addition, changes in the mechanical environment induce reorganization of the SFs. Recently, we noticed that the SF networks reappeared following their temporal disruption with cytochalasin D looked similar to those before disruption in rat aortic smooth muscle cells (RASMs). This indicates that the cells may have a memory of SF orientation. The aim of this study was to clarify the mechanism of the memory particularly focusing on the effects of microtubules (MTs) and focal adhesions (FAs) during the reorganization process of SFs. Firstly, we preconditioned the cells with cyclic stretch to make their SFs align in a uniform direction. After cyclic stretching, we depolymerized SFs completely with cytochalasin D for 3 h, and let them repolymerize in the drug free medium for 3 h. To know the effects of MTs during the SF repolymerization, we depolymerized MTs with colchicine. FAs were observed with a surface reflective interference contrast microscopy. In the presence of MTs, repolymerized SFs appeared in random orientation with newly formed FM, while FM were not destroyed and the alignment of SFs was conserved in the absence of MTs. The conservation of FAs might serve as a memory of SF alignment., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2008

527 Analysis of stress fiber reorientation in osteoblast-like cells induced with cyclic stretch : The effects of cyclic stretch waveform and cell junctions
NAGAYAMA Kazuaki; KIMURA Yuki; MATSUMOTO Takeo, It has been reported that the stress fibers (SFs) of cells on elastic substrate aligned at a particular angle so as to minimize their strain magnitude caused by cyclic deformation of the substrate. However, little is known about the mechanism of their alignment. In this study, we investigated the effects of cyclic stretch waveform and intercellular junctions on the SF alignment in MC3T3-E1 osteoblast-like cells. The cells were cultured on silicone membranes under a sparse (15 cells/mm^2) or dense (300 cells/mm^2) condition, and subjected to cyclic uniaxial stretch having either one of the following wave forms with an amplitude of 8%: triangular; trapezoid, bottom hold, or peak hold for 24 h. Alignment of their SFs were then analyzed with a two-dimensional Fourier transformation analysis. In the sparse condition, no orientation was observed for the triangular and the peak hold waveforms, while SFs aligned mostly in the direction in which normal strain of substrate becomes zero (〜54°) with other waveforms, especially with the trapezoid waveform which had a hold time both at the maximum strain and the zero-strain state. Intracellular SFs generate a prestress, and they depolymerize with release of their prestress. They are also viscoelastic. Thus our results indicate that depolymerization and reorientation of SFs were significantly accelerated with the release of their prestress caused by the stress relaxation of SFs during the hold times in the trapezoid waveform. In the dense condition, in which cells have intercellular junctions, SFs aligned in perpendicular to and/or parallel to the stretch direction with the triangle waveform and in perpendicular to the stretch direction with other waveforms, as if the cells avoided shear deformation causing breakdown of cell-cell junctions. These results indicate that time history of stress applied to the SFs as well as intercellular junctions may have profound effects on cell alignment in MC3-3-E1 cells., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2008

755 Noninvasive measurement of pressure-diameter relationship of human brachial artery: An attempt
MATSUMOTO Takeo; HIRATA Satoshi; TAKEZAWA Kenji; MASUDA Hiroshi; NAGAYAMA Kazuaki, A novel method to obtain pressure-diameter relationship of human brachial artery noninvasively in a wide pressure range was proposed. An airtight box was installed on the forearm and its inner pressure was changed from -100 to +150 mmHg to change transmural pressure of the artery. Inflation and deflation of the artery due to transmural pressure change was monitored with an ultrasound probe attached in the box. When the artery was collapsed by pressurizing the box and then returned to the initial state, its diameter in the physiological state increased, while it decreased following temporal overload to the artery, i.e., temporal negative pressure application in the box. These changes may be caused by the active response of the smooth muscle cells in the media, i.e., Bayliss effect, and are not observed in excised arteries. In vivo measurement of mechanical properties of the arteries is important., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2008

力学的刺激による細胞機能制御の試み:繰返引張刺激ならびに基板弾性率の違いが細胞形態および分化へ与える影響
長山 和亮; 石黒 真衣; 渥美 佳則; 松本 健郎, The Society of Life Support Engineering
ライフサポート, 2008

Effects of pre-impact body orientation on traumatic brain injury in a vehicle-pedestrian collision
Tamura A; Nakahira Y; Iwamoto M; Nagayama K; Matsumoto T, A series of minivan-pedestrian collisions was simulated, and pre-impact body orientation was found to considerably affect the mechanical responses of injury predictors for traumatic brain injury (TBI). The maximum average traction force generated in the cervical spinal cord prior to head strike took its peak value when the pedestrian was subjected to purely lateral head rotation in a sideways collision and decreased by up to one-half in a symmetric manner as the pedestrian changed his direction toward or away from the vehicle. The intracranial strain concentration and the cumulative strain damage measure following the head strike increased by more than 60% as the initial pedestrian configuration changed from the backward to frontal collision. Since the outcome of injury predictors is closely associated with an initial body facing angle to the striking vehicle, regulatory impactor tests should consider the effects of pre-impact body orientation for accurately assessing real-world TBIs in the future. Copyright © 2008, Inderscience Publishers.
International Journal of Vehicle Safety, 2008, [Reviewed]

Mechanical Characterization of Brain Tissue in High-Rate Extension
Tamura A; Hayashi S; Nagayama K; Matsumoto T, Mechanical properties of brain tissue characterized in high-rate loading regime are indispensable for the analysis of traumatic brain injury (TBI). However, data on such properties are very limited. In this study, we measured transient response of brain tissue subjected to high-rate extension. A series of uniaxial extension tests at strain rates ranging from 0.9 to 25 s−1 and stress relaxation tests following a step-like displacement to different strain levels (15–50%) were conducted in cylindrical specimens obtained from fresh porcine brains. A strong rate sensitivity was found in the brain tissue, i.e., initial elastic modulus was 4.2 ± 1.6, 7.7 ± 4.0, and 18.6 ± 3.6 kPa (mean ± SD) for a strain rate of 0.9, 4.3, and 25 s−1, respectively. In addition, the relaxation function was successfully approximated to be strain-time separable, i.e., material response can be expressed as a product of time-dependent and strain-dependent components as: K(t) = G(t)σe(ε), where G(t) is a reduced relaxation function, G(t) = 0.416e−t/00096 + 0.3 27e−t/00138 + 0.256e−t/1.508, and σe (ε) is the peak stress following a step input of ε. Results of the present study will improve biofidelity of computational models of a human head and provide useful information for the analysis of TBI under injurious environments with strain rates greater than 10 s−1. © 2008, The Japan Society of Mechanical Engineers. All rights reserved.
Journal of Biomechanical Science and Engineering, 2008, [Reviewed]

Microscopic mechanical analysis of aortic wall: Estimation of stress in the intramural elastic laminas and smooth muscle cells in a physiological state
Takeo MATSUMOTO; Akira FUKUNAGA; Kengo NARITA; and Kazuaki NAGAYAMA, Last, AMER SOC MECHANICAL ENGINEERS
Proceedings of the 2008 Summer Bioengineering Conference, 2008, [Reviewed]

On the Intracellullar Memory of Stress Fiber Orientation: Effects of Microtubules and Focal Adhesions on the Repolymerization Process of Stress Fibers
Yunfeng YANG; Kazuaki NAGAYAMA; and Takeo MATSUMOTO, AMER SOC MECHANICAL ENGINEERS
Proceedings of the 2008 Summer Bioengineering Conference, 2008, [Reviewed]

〔Major achievements〕Actin Filaments Affect Not Only Elasticity But Also Late Viscous Response in Stress Relaxation of Single Isolated Aortic Smooth Muscle Cells (Possible Effect of Active Reorganization of Actin Filaments)
Nagayama K; Yanagihara S; and Matsumoto T, Lead, The stress relaxation test was performed for cultured rat aortic smooth muscle cells (SMCs) to investigate the effect of actin filaments (AFs) on viscoelastic properties of the cells. Untreated cells and cells treated with cytochalasin D to disrupt their AFs were stretched by 70-85%, and their length was kept constant with a laboratory-made micro tensile tester with feed-back control to obtain their stress relaxation curve. Viscoelastic analysis with 4-parameter Maxwell model showed that the stress relaxation process of the cells could be divided into two phases with different time constants: a fast phase with a time constant in the order of minutes, and a slow phase with a time constant in the order of hours. Elastic parameters in the two phases decreased similarly by about a half with AF disruption. Viscous parameters also decreased by ∼1/3 and ∼1/4 in the fast and the slow phase, respectively, with AF disruption. No difference was observed for the relaxation time constant in the fast phase in response to AF disruption, while the time constant in the slow phase decreased significantly by about a half. Fluctuation in tension was observed in the stress relaxation curve of the untreated cells. Such fluctuation disappeared in cells treated with cytochalasin D. These results indicates that AFs have significant effects on viscosity of SMCs in the slow phase and on the fluctuation in tension, both of which may be caused by the dynamic change of AFs., The Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 01 Sep. 2007, [Reviewed]

1005 Effects of extracellular Ca^<2+> on stress relaxation properties of single isolated aortic smooth muscle cells
NAGAYAMA Kazuaki; SAITO Shunsuke; MATSUMOTO Takeo, Stress relaxation response at the whole-cell level was studied in rat aortic smooth muscle cells (SMCs). SMCs adhering to the bottom of culture dish were held with a pair of micropipettes maintaining its in situ shape and cytoskeletal integrity. Stress relaxation test at constant strain was performed using a laboratory made micro tensile tester with pipette position feed-back control. SMCs were stretched stepwise by 30% from no-load length, and their length was kept constant for 1200s in Ca^<2+> -rich (5mM) and Ca^<2+> free condition in order to investigate the effects of extracellular Ca^<2+> on their viscoelastic properties. The stress decreased exponentially and reached a plateau in 〜300s for the majority of cells. The average stress were 〜3 times larger in the Ca^<2+> -rich condition than in the Ca^<2+> -free in all range of the stress relaxation. Although the difference in the relaxation rate was insignificant in the two groups, the stress relaxation curves were more uniform in Ca^<2+> -rich condition. These results indicate that extracellular Ca^<2+> may increase intracellular stress possibly through activating actomyosin contractility, and stabilize the viscoelastic properties of SMCs., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2007

Variation in nerve fiber strain in brain tissue subjected to uniaxial stretch
Tamura A; Hayashi S; Nagayam K; Matusmoto T, Diffiisc axonal injury (DAI) is the most frequent type of closed head injury involved in vehicular accidents, and is characterized by structural and functional damage of nerve fibers in the white matter that may be caused by their overstretch. Because nerve fibers in the white matter have a undulated network-like structure embedded in the neuroglia and extracellular matrix, and are expected to be much stiffer than other components, the strain in the nerve fiber is not necessarily equal to that in the white matter. In this study, the authors have measured strain of the nerve fibers running in various directions in porcine brain tissue subjected to uniaxial stretch and compared them with global strain (tissue strain). The nerve fiber strain had a close correlation with their direction, and was smaller than surrounding global strain. Tensile strain appeared fit the fibers ranging from 0 to 60 degrees relative to stretch direction while strain was compressive in those ranging from 60 to 90 degrees. The tensile and compressive strain at maximum stretch was 0.07 and -0.03, respectively, for nerve fibers, while it was 0.33 and -0.12, respectively, for the whole tissue. Roughly speaking, the maximum neural fiber strain was similar to 1/3 of its surrounding tissue strain in respective fiber direction, indicating that the local strain in the neural fibers is not equal to global strain in the brain tissue. Consideration of neural fiber alignment in the white matter is important in studying the mechanical aspects of pathogenesis in DAI., SOC AUTOMOTIVE ENGINEERS
Stapp Car Crash Journal, 2007, [Reviewed]

Mechanical characterization of brain tissue in high-rate compression
Tamura A; Hayashi S; Watanabe I; Nagayama K; Matsumoto T, Mechanical properties of brain tissue in high strain region are indispensable for the analysis of brain damage during traffic accidents. However, accurate data on the mechanical behavior of brain tissue under impact loading condition are sparse. In this study, mechanical properties of porcine brain tissues were characterized in their cylindrical samples cored out from their surface. The samples were compressed in their axial direction at strain rates ranging from 1 to 50 s^-1. Stress relaxation test was also conducted following rapid compression with a rise time of ∼30 ms to different strain levels (20-70%). Brain tissue exhibited stiffer responses under higher impact rates: initial elastic modulus was 5.7±1.6, 11.9±3.3, 23.8±10.5 kPa (mean±SD) for strain rate of 1, 10, 50 s^-1, respectively. We found that stress relaxation K(t,ε) could be analysed in time and strain domains separately. The relaxation response could be expressed as the product of two mutually independent functions of time and strain as:
K(t,ε)=G(t)σ^e(ε), where σ^e(ε) is an elastic response, i.e., the peak stress in response to a step input of strain ε, and G(t) is a reduced relaxation function:
G(t)=0.642e^-t/0.0207+0.142e^-t/0.482+0.216e^-t/18.9, i.e., the time-dependent stress response normalized by the peak stress. The reduced relaxation function obtained here will serve as a useful tool to predict mechanical behavior of brain tissue in compression with strain rate greater than 10 s^-1., The Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 2007, [Reviewed]

Mechanical analysis of the aortic wall considering microscopic heterogeneity　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Akira FUKUNAGA; Kengo NARITA; and Kazuaki NAGAYAMA
Proceedings of the 1st IMACS (International Association for Mathematics and Computers in Simulation) International Conference on Computational Biomechanics and Biology (ICCBB 2007), 2007

〔Major achievements〕Effect of Actin Filament Distribution on Tensile Properties of Smooth Muscle Cells Obtained from Rat Thoracic Aortas
Nagayama K; Nagano Y; Sato M; Matsumoto T, Lead, Tensile properties and actin filament distribution of rat aortic smooth muscle cells (SMCs) were measured in the same cells to correlate the mechanical properties of cells with their cytoskeleton. The cells freshly isolated from rat thoracic aorta with enzymatic dispersion (FSMCs), cultured cells (CSMCs), and CSMCs treated with cytochalasin D to disrupt their actin filaments (CSMCs-CYD) were stretched in a Ca2+-Mg2+-free Hank's balanced salt solution at 37 degrees C with an originally designed micro tensile tester. Some of CSMCs and CSMCs-CYD were fixed and stained with rhodamine phalloidin for actin filament after the tensile test while they remained attached to the tester. The force-elongation curves were almost linear for all of the three groups. Normalized stiffness E-all obtained from the slope of the curves was significantly different among groups and was 11.0 +/- 1.9 kPa (mean +/- SEM, n = 8), 2.6 +/- 0.5 kPa (n = 21), 1.5 +/- 0.2 kPa (n = 13), for FSMCs, CSMCs, and CSMCs-CYD, respectively. Relative concentration of the actin filament in the central region of the cell F has significant positive correlation with E-all both for CSMCs and CSMCs-CYD. The slope of the regression line Delta E-all/Delta F was much higher in the CSMCs than in the CSMCs-CYD. These results indicate that elastic properties of smooth muscle cells may be affected not only by the amount of their actin filaments, but also by their organization and distribution in cells. (C) 2004 Elsevier Ltd. All rights reserved., ELSEVIER SCI LTD
Journal of Biomechanics, 03 Aug. 2006, [Reviewed]

細胞把持回転観察システムの開発とこれを用いた細胞内微細構造の3次元構造観察
和家 史知; 小川 雅之; 長山 和亮; 松本 健郎, The Society of Life Support Engineering
ライフサポート, 05 Jul. 2006

〔Major achievements〕Tensile Properties of Cultured Aortic Smooth Musle Cells Obtained in a Quasi-in situ Tensile Test with Thermoresponsive Gelatin
Nagayama K; Tsugawa A; Matsumoto T, Lead, We established a quasi-in situ tensile test to measure the tensile properties of smooth muscle cells (SMCs) cultured on substrate maintaining their shape and cytoskeletal integrity. SMCs were cultured on a substrate coated with thermoresponsive gelatin (PNIPAAm-gelatin) and were held with a pair of micropipettes coated with an adhesive. Cells were detached from the substrate by lowering ambient temperature to dissolve the PNIPAAm-gelatin. Tensile tests for fusiform SMCs up to ∼15% strain performed 3 times in normal and Ca²⁺-free Hank's balanced salt solution (HBSS(+) and HBSS(-), respectively) in order to investigate the effects of Ca²⁺ on the change in their tensile properties during loading/unloading cycles. The stiffness of the fusiform SMCs obtained by the first loading process in HBSS(-) and in HBSS(+) was 0.041±0.024 N/m (n=6, mean±SEM) and 0.031±0.008 N/m (n=6), respectively, and was significantly lower than that of spherical cells detached from the substrate by trypsinization (∼0.09 N/m), indicating that cell stiffness is overestimated when cells are trypsinized. Cell stiffness increased from the first cycle to the second and then stabilized in HBSS(-), while it increased continuously with the number of the cycles in HBSS(+). These results suggest that the mechanical properties of SMCs change with stretching and that extracellular Ca²⁺ has a significant effect on their response to stretch., The Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 10 Jun. 2006, [Reviewed]

〔Major achievements〕A Novel Micro Tensile Tester with Feed-back Control for Viscoelastic Analysis of Single Isolated Smooth Muscle Cells
Nagayama K; Yanagihara S; Matsumoto T, Lead
Medical Engineering & Physics, 01 May 2006, [Reviewed]

Microscopic Analysis of Residual Stress and Strain in the Aortic Media Considering Anisotropy of Smooth Muscle Layer
Matsumoto T; Furukawa T; Nagayama K
Proceedins of the IUTAM Symposium on Mechanics of Biological Tissue 2004, Mar. 2006

709 Effects of cytoskeletons on tensile properties of cultured aortic smooth muscle cells obtained in a quasi-in situ tensile test
NAGAYAMA Kazuaki; TSUGAWA Akira; MATSUMOTO Takeo, Effects of actin filaments (AFs) and microtubules (MTs) on quasi-in situ tensile properties and internal tension at a whole-cell level were studied in rat aortic smooth muscle cells (SMCs) cultured on substrates. SMCs were held with a pair of micropipettes maintaining their shape on the substrate. Tensile tests up to〜10% strain were performed for 3-4 times both before and after administration of cytochalasin D or colchicine. Force-elongation curves became stable after second cycle of loading/unloading process. The cell stiffness defined as the average slope of loading curve in stable loops were decreased by〜70% after AF disruption with cytochalasin D. Treatment with colchicine, a MT disrupter, decreased cell stiffness by〜30%. The cell height significantly increased with AF disruption, while it decreased with MT disruption. These results indicate that not only AFs but also MTs play crucial roles in maintaining whole-cell stiffness of SMCs, and while AFs act as an internal tension generator, MTs may act as a tension reducer., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2006

747 Effect of Cells on the Change in the Mechanical Properties of Bone Tissue during Cyclic Compression Culture
ICHIKAWA Katsuhisa; NAKAGAKI Masashi; NAGAYAMA Kazuaki; MATSUMOTO Takeo, We found that the stiffness of bone tissues cultured under cyclic compression increased significantly. But it was not clear whether this change was an active adaptation of the cells in bone or it was just a passive change of the tissue. To clarify this, bone tissues including those treated with liquid nitrogen to kill cells were cultured under cyclic compression. Cell viability was measured in specimens cultured in various conditions. The stiffness of bone tissues without living cells did not increase. Thus, we confirmed that the stiffening of the specimens exposed to cyclic compression culture is an active change in the bone tissue., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2006

740 3-D Observation of Cell Nucleus and Cytoskeleton with Cell Rotation System
OGAWA Masayuki; WAKE Fuminori; NAGAYAMA Kazuaki; ISHINO Yojiro; MATSUMOTO Takeo, A cell rotation system (CRS) has been developed to observe three dimensional (3D) morphology of cells precisely from their images obtained from various points of view. In this system, a cell held with a micropipette under a microscope is rotated around the axis of the micropipette set perpendicular to the optical axis, while the pipette tip is kept in position based on the binarized image of the pipette tip. In this study, distributing back projection (DBP) method that is one of the computerized tomography (CT) algorithms is applied to obtain clear 3D images of intracellular structure such as nucleus and cytoskeleton. The reconstructed images were clear and we could observe details of 3D structures of nucleus and actin filaments. The 3D reconstruction with CRS would become a powerfull tool for detailed observation of various intracellular structures., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2006

633 Effect of Microscopic Residual Stress on the Corrugation of Elastic Lamina of Elastic Arteries Under No Load Condition
FUKUNAGA Akihisa; NAGAYAMA Kazuaki; YOSHIMURA Atsushi; MATSUMOTO Takeo, Elastic laminas (ELs) in unloaded elastic arteries are usually corrugated. In this study, we examined whether the corrugation could be caused by the compressive residual stress residing in the ELs. Corrugation was evaluated by a waviness, the length along corrugation divided by the length along global curvature of ELs. Waviness in ring-like specimens decreased from 1.32 to 1.27 in the internal elastic lamina (IEL) upon radial cutting to release macroscopic residual stress. After the specimens were frozen and thawed to disrupt smooth muscle cells bearing tensile stress, waviness decreased further to 1.24 in the IEL, corresponding to the release of microscopic residual stress. Waviness decreased again when ELs were dissected from surrounding tissues, and decreased further when the surrounding tissues were removed completely with collagenase treatment. These results may indicate that ELs were compressed by the surrounding tissues including smooth muscle cells to form their corrugation., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2006

Effects of actin filaments on anisotropy and stiffness of aortic smooth muscle cells
T. Matsumoto; K. Nagayama, Actin filaments have been reported to be -1000 times stiffer than whole cells. Thus, they must play major roles in mechanical properties of cells. Effects of actin filament distribution and alignment on anisotropy and stiffness were studied on rat aortic smooth muscle cells. Freshly isolated cells (FSMCs), cultured cells (CSMCs), and CSMCs treated with cytochalasin D to disrupt their actin filaments (CSMCs-CYD) were stretched with an originally designed micro tensile tester. FSMCs were stretched in their major and minor axes directions to evaluate their anistropy. The normalized stiffness of FSMCs was significantly higher in the major axis (14.8±4.3kPa, mean±SEM, n=5) than the minor axis (2.8±1.0kPa, n=5). Long and thick fibers of actin filament were found running almost parallel to the major axis of the cells, indicating increased stiffness in this direction. CSMCs and CSMCs-CYD were stained for actin filament after the tensile test while they remained attached to the tester. Relative concentration of the actin filament in the central region of the cell F had significant positive correlation with normalized stiffness in both cells. These results indicate that elastic properties of smooth muscle cells are affected not only by the amount of their actin filaments, but also by their organization and distribution in cells., World Scientific Publishing Co.
Biomechanics at Micro- and Nanoscale Levels, 01 Jan. 2006, [Reviewed]

Measurement of nerve fiber strain in brain tissue subjected to uniaxial stretch (Comparison between local strain of nerve fiber and global strain of brain tissue)
Tamura A; Nagayama K; Matsumoto T, Diffuse axonal injury (DAI) is a specific type of closed head injury often seen in automobile accidents, that directly leads to the morbidity and mortality, however, the injury mechanism of DAI has yet to be clarified. DAI is characterized by structural and functional damage in nerve fibers in the white matter, which may be caused by excessive tensile strain. While the white matter has a network-like structure of nerve fibers embedded in neuroglia and the extracellular matrix, the nerve fibers are undulated and the mechanical properties of these components are not necessarily equal. Thus, the strain in the white matter can be different from that in the fibers. In this study, we have measured stretch ratios of the nerve fibers running in various directions in porcine brain tissue subjected to uniaxial stretch and compared them with global strain. It was found that the fiber direction positively correlated with neural fiber strain whilst the fiber strain was not equal to global strain. Particularly, the maximum neural fiber strain was ∼25% of its surrounding tissue strain, indicating that the local strain in the neural fibers is not equal to global strain in the brain tissue. Consideration of neural fiber alignment in the white matter is important in studying the mechanical aspects of pathogenesis of DAI., The Japan Society of Mechanical Engineers
Journal of Biomechanical Science and Engineering, 2006, [Reviewed]

EFFECTS OF ACTIN FILAMENTS ON THE VISCOELASTIC PROPERTIES OF AORTIC SMOOTH MUSCLE CELLS　　　　　　　　　　　　　　　
Nagayama K; Yanagihara S and Matsumoto T, Lead
Proceedings of 15th International Conference on Mechanics in Medicine and Biology (ICMMB-15), 2006, [Reviewed]

〔Major achievements〕Observation of cell shortening and dynamic changes of actin filaments during cell detachment from thermoresponsive-gelatin-coated substrate
Nagayama K; Matsumoto T, Lead, We observed cell shortening and dynamic changes of actin filaments during detachment from the substrate by using a thermoresponsive-gelatin. The thermoresponsive-gelatin, a mixture of the poly(N-isopropylacrylamide) grafted gelatin (PNIPAAm-grafted-gelatin) and PNIPAAm, was coated on the glass bottom culture dishes. Rat aortic smooth muscle cells (SMC) expressed GFP-actin were cultured on the thermoresponsive-gelatin-coated dishes filled with serum free Dulbecco's Modified Eagle's medium (DMEM) or Ca2+-Mg2+-free Hank's balanced salt solution (HBSS(-)). They adhered normally at 37 degrees C, and became shortened and detached from the dishes when the ambient temperature was dropped below 34 degrees C due to melting of the gelatin substrate. The shortening of SMCs was larger in DMEM (51.0 +/- 3.0%, mean +/- SEM, n = 14) than in HBSS(-) (35.8 +/- 3.6%, n = 14). Actin filaments remained straight during detachment in HBSS(-), while in DMEM, they locally concentrated and disappeared at cell periphery. The shortening of SMCs upon detachment from ordinary plastic culture dishes by trypsinization was more than for both media. No significant difference was observed between the two, indicating detrimental effects of the trypsin. The present method was useful to study the cell contraction and the actin filament behavior during cell detachment for this causes minimal damage to cells., JAPAN SOC MECHANICAL ENGINEERS
JSME Int. J, Ser C, 10 May 2005, [Reviewed]

1244 A Cell Rotation System with Flexible Cell Access Mechanism and Real-time Pipette Position Control
WAKE Fuminori; NAGAYAMA Kazuaki; MATSUMOTO Takeo, A cell rotation system (CRS) has been developed to observe three dimensional (3D) morphology of cells precisely from their images obtained from various points of view. In this system, cell held with a micropipette under a microscope is rotated around the axis of the micropipette set perpendicular to the optical axis, while the pipette tip is kept in position based on the binarized image of the pipette tip. The displacement range of the pipette tip was narrow in the previous system. In this study, a lever mechanism was introduced to widen the displacement range. We also introduced a flexible cell access mechanism capable of holding an arbitrary cell on a slide glass. In addition, we have succeeded in the real-time pipette tip position control by using feedback control in combination with feedforward control., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2005

231 Observation of intracellular microstructural behavior in contraction process of vascular smooth muscle cells
NAGAYAMA Kazuaki; TSUGAWA Akira; MATSUMOTO Takeo, The Japan Society of Mechanical Engineers
Proceedings of the JSME Bioengineering Conference and Seminar, 2005

506 Development of a probe-type viscoelastometer for human skin
HIRAI Takashi; YAGI Motoomi; NAGAYAMA Kazuaki; MATSUMOTO Takeo, The Japan Society of Mechanical Engineers
Proceedings of the JSME Bioengineering Conference and Seminar, 2005

230 Development of a cell tensile tester with feedback control and measurement of the viscoelastic properties of cultured smooth muscle cells
YANAGIHARA Shinichiro; TSUGAWA Akira; NAGAYAMA Kazuaki; MATSUMOTO Takeo, The Japan Society of Mechanical Engineers
Proceedings of the JSME Bioengineering Conference and Seminar, 2005

439 Continuous monitoring of mechanical properties of bone tissues in culture under cyclic compression
NAKAGAKI Masashi; OIWA Mikio; SUGIYAMA Takahiko; NAGAYAMA Kazuaki; MATSUMOTO Takeo, The Japan Society of Mechanical Engineers
Proceedings of the JSME Bioengineering Conference and Seminar, 2005

544 Microscopic analysis of mechanical environment in the wrinkled skin of UV-irradiated mice
IKUTA Naoko; ORI Mako; NAGAYAMA Kazuaki; AMANO Satoshi; MATSUMOTO Takeo, The Japan Society of Mechanical Engineers
Proceedings of the JSME Bioengineering Conference and Seminar, 2005

Relation between morphology and protein expression of mouse bone marrow cells to cyclic stretch
ATSUMI Yoshinori; ISHIGURO Mai; NAGAYAMA Kazuaki; MATSUMOTO Takeo, The Society of Life Support Engineering
Journal of Life Support Technology, 2005

The effect of cytoskeletal structures on the viscoelastic properties of aortic smooth muscle cells
Nagayama Kazuaki; Yanagihara Shinichiro; Matsumoto Takeo, The Society of Life Support Engineering
Journal of Life Support Technology, 2005

Circumferential Heterogeneity in Contractile Properties of Smooth Muscle Cells in Rabbit Thoracic Aortas　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Takahiro SHIRONO; and Kazuaki NAGAYAMA, Last
Proceedings of the 12th International Conference on Biomedical Engineering (ICBME05) ), 2005

A Cell Rotation System for the Observation of 3D Microstructure of Cells　　　　　　　　　　　　　　　
Takeo MATSUMOTO,Hideki TAJIMA; Norikazu ITO; Kazuaki NAGAYAMA; and Masaaki SATO
Proceedings of the 2005 Summer Bioengineering Conference, 2005, [Reviewed]

An Improved Cell Rotation System for 3D Analysis of Cell Morphology　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Fuminori WAKE; and Kazuaki NAGAYAMA
Proceedings of the 6th Asian-Pacific Conference on Biomedical Engineering, 2005

A Newly Designed Micro Tensile Tester with Feed-back Control for Viscoelastic Analysis of Single Isolated Smooth Muscle Cells　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; Shinichiro YANAGIHARA; and Takeo MATSUMOTO, Lead
Proceedings of the 2005 Summer Bioengineering Conference, 2005, [Reviewed]

Effect of Actin Filament Orientation on Mechanical Anisotropy of Freshly-Isolated Vascular Smooth Muscle Cells　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; and Takeo MATSUMOTO, Lead
Proceedings of the 6th Asian-Pacific Conference on Biomedical Engineering, 2005

〔Major achievements〕Development of newly designed atomic force microscope system for measuring of mechanical properties of cells　　　　　　　　　　　　　　　
Nagayama K,Sasaki M,Hane K,Sato M,Matsumoto T, Lead
Trans Jpn Soc Mech Engineers Ser C 70, 128-134 (2004) [In Japanese], 12 May 2004, [Reviewed]

〔Major achievements〕細胞用二軸繰返引張機構の開発とこれを用いた血管内皮細胞の力学応答の解析　　　　　　　　　　　　　　　
中垣将; 柳原辰一郎; 長山和亮; 松本健郎
日本機械学会論文集Ａ編, 12 May 2004, [Reviewed]

〔Major achievements〕Mechanical Anisotropy of Rat Aortic Smooth Muscle Cells Decreases with Their Contraction: Possible Effect of Actin Filament Orientation
Nagayama K and Matsumoto T, Lead, Tensile properties of smooth muscle cells freshly isolated from rat thoracic aortas (FSMCs) in their major and minor axes were measured using a laboratory-made micro tensile tester. The relationship between the tension applied to a cell and its elongation was obtained in untreated cells and those treated with 10(-5) M serotonin to induce contraction. An initial stiffness of untreated FSMCs, normalized by their initial cross-sectional area perpendicular to the stretch direction, was significantly higher in the major axis (14.8 +/- 4.3 kPa, mean SEM, n = 5) than the minor axis (2.8 +/- 1.0 kPa, n = 5). The stiffness increased significantly in response to the contraction, but the increase was much higher in the minor axis (59.0 +/- 9.4 kPa, n = 4) than in the major (88.1 +/- 13.3 kPa, n = 4). The difference between the two directions was insignificant in the contracted state. Observations of the morphology of actin filaments with a confocal laser scanning microscope in untreated FSMCs revealed that they were long fibers running almost parallel to the major axis, while those in contracted cells showed an aggregated structure without a preferential direction. These results may indicate that anisotropy in untreated FSMCs is caused by the anisotropic alignment of their actin filaments, and that such anisotropy disappears in response to actin filament reorganization caused by the contraction., JAPAN SOC MECHANICAL ENGINEERS
JSME Int J, Ser C, 15 Apr. 2004, [Reviewed]

Development of a biaxial cyclic stretching mechanism and its use for the analysis of mechanical response of vascular endothelial cells
Masashi Nakagaki; Shinichiro Yanagihara; Kazuaki Nagayama; Takeo Matsumoto, Study on the cellular responses to biaxial cyclic stretch requires a complex device giving two dimensional deformations to cell substrates. To carry out the biaxial testing easily, we have developed a mechanism that makes a conventional uniaxial device to biaxial one. By incorporating two three-bar linkages into a conventional uniaxial device NS-300, we obtained cyclic stretching motion perpendicular to its original stretch direction. Difference in the displacement between the two directions was less than 1.4% for a 10% stretching mode. By changing the linkage assembly, we can select two modes of biaxial stretching : simultaneous and alternate. The deformation of the silicone membrane on the bottom of a newly developed biaxial chamber was almost uniform in the central region of 12 mm × 12 mm. We applied various modes of biaxial and uniaxial cyclic stretches to bovine aortic endothelial cells with this device, and found that the cells aligned in the direction with minimal substrate deformation, a well-known cellular response to cyclic stretch. This device is useful in studying cellular response to biaxial stretching for its easiness in extending capability of conventional uniaxial stretch devices to biaxial ones., Japan Society of Mechanical Engineers
Nippon Kikai Gakkai Ronbunshu, A Hen/Transactions of the Japan Society of Mechanical Engineers, Part A, 2004

Multiscope analysis of circumferential heterogeneity in wall deformation of thoracic aortas in response to smooth muscle contraction
SHIRONO Takahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo, We have investigated the circumferential heterogeneity of the smooth muscle (SM) contraction in this artery wall from two viewpoints. From a macroscopic viewpoint, we measured the deformation of the artery wall following SM contraction in four circumferential positions to find that the ventral section contracted more than the dorsal (P<0.005). From a microscopic viewpoint, the SM cells were isolated from the ventral and the dorsal regions by enzymatic digestion to compare the contractility of the cells obtained from the different circumferential positions. All cells isolated from the ventral side become shorter than 40μm upon contraction, while about 8% of the cells obtained from the dorsal side remained elongated even after the stimulation with 10^<-5>M norepinephrine. These results may indicate that 1) the population of the smooth muscle cells is heterogeneous; 2) less contractile cells reside in the dorsal side of the aortic wall, causing the circumferential heterogeneity, in the contraction., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2004

Measurement of Contractile Properties and Intracellular Distribution of Actin Filaments in Freshly-isolated Vascular Smooth Muscle Cells
NAGAYAMA Kazuaki; YANAGIHARA Shinichiro; SHIRONO Takahiro; MATSUMOTO Takeo, Contractile properties and actin filament morphology were measured in smooth muscle cells freshly isolated from rat thoracic aortas. The major length of the cells before and after contraction induced with 10^<-5>M serotonin was 49.0 ± 5.6 μm (n=7, mean ± SEM) and 39.2 ± 5.4 μm, respectively, and the cell shortening was 20.1 ± 3.9 %. The cell shortening increased with their initial cell length, peaked at 〜50 μm, and then decreased. The actin filaments in the untreated cells were mostly straight fibers running along the major axis of the cells, while those in the contracted cells. had aggregated structure without preferential direction. The volume and the average fluorescent intensity of the actin filaments estimated from their confocal images were not significantly different between the untreated and the contracted cells. These results may indicate that the cell contraction is accompanied not only by the sliding of actin and myosin filaments but also by the entanglement of the actin filaments, maintaining the amount of actin filaments., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2004

Effect of Actin Filament on Tensile Properties of Rat Aortic Smooth Muscle Cells　　　　　　　　　　　　　　　
Matsumoto T; Nagayama K; Nagano Y; Sato M, Lead
Proceedings of the First Asian Pacific Conference on Biomechanics, 2004

Development of a cell rotation system for the observation of 3D microstructure of cells　　　　　　　　　　　　　　　
Takeo MATSUMOTO,Hideki TAJIMA; Norikazu ITO; Kazuaki NAGAYAMA; and Masaaki SATO
Proceedings of Workshop on Biomechanical Engineering and Biomaterials, 2004

Tensile Properties and Distribusion of Intracellular Actin Filaments Measured in Cultured Smooth Muscle Cells Obtained from Rat Thoracic Aorta
NAGAYAMA Kazuaki; NAGANO Yujiro; SATO Masaaki; MATSUMOTO Takeo, We have measured and compared tensile properties of cultured smooth muscle cells (CSMCs) obtained from rat thoracic aortas, and those of the CSMCs whose actin filament networks had been disrupted with cytochalasin D (CSMCs-CYD). Tensile properties of these cells were measured using a micro tensile tester developed in our laboratory. A cell in a dish was held with two glass micropipettes, an operation pipette and a deflection pipette. The operation pipette was moved with a computer-controlled electrical manipulator to stretch the cell horizontally. The rate of pipette movement was set to keep the strain rate in each cell within the range of 0.6-3%/s, in which the elastic modulus did not change significantly in our system. The force applied to the cell was measured by the deflection of the cantilever part of the deflection pipette. We have also observed their actin filament distribution while the cells remained stretched after the tensile test. The actin filament concentration in the central region of the cells had significant correlation with their elastic modulus., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2003

Uniaxial tensile properties of horny layer, epidermis and dermis of guinea pigs
MATSUMURA Yoshiko; IKUTA Naoko; NAGAYAMA Kazuaki; MATSUMOTO Takeo, Human skin consists of the horny layer, living epidermis and dermis. Because their histology and constituents are different among the layers, the mechanical properties of each layer may also differ. However, there have been few studies on the difference among these layers. In this study, we measured the uniaxial tensile properties of the horny layer, epidermis and dermis of the guinea pigs. The tensile test was performed in the physiological saline solution at 37℃. With regard to the horny layer, the test was also performed in the air at room temperature with the humidity of about 75% and 15%. In the physiological saline solution, the elastic modulus of the horny layer was 180kPa, epidermis 130kPa, and dermis 80kPa. Based on these values and the thickness of each layer, the elastic modulus of living epidermis was estimated to be 70kPa. The elastic modulus of the horny layer depended strongly on the humidity, and was 720kPa at 70% and 10MPa at 15%. These results suggest that the mechanical properties of the skin are different among layers, and the horny layer is much stiffer than other two layers., The Japan Society of Mechanical Engineers
The proceedings of the JSME annual meeting, 2003

〔Major achievements〕Local mechanical properties measured by atomic force microscopy for cultured bovine endothelial cells exposed to shear stress
Masaaki SATO; Kazuaki NAGAYAMA; Noriyuki KATAOKA; Minoru SASAKI; and Kazuhiro HANE, Morphology and mechanical properties of cultured endothelial cells were measured, using a novel atomic force microscope (AFM) system, developed in our laboratory, in conjunction with an inverted confocal laser scanning microscope. We used this system to examine endothelial cell both in static cultures and exposed to a shear stress of 2 Pa. Initially, the three-dimensional topography of a cell was measured by the AFM and a location was selected for the subsequent measurement of the mechanical response of the cell. The surface of statically cultured cell was smooth. The cell height was not altered by the exposed duration of shear stress. A relationship between external force, F, and the indentation depth, delta, was obtained for several different locations on a cell. This force-indentation response was modelled using a quadratic equation, F = a delta(2) + b delta, indicating that two parameters, a and b, will be constants which are representative of the mechanical response. Endothelial cells cultured at static conditions demonstrated a polygonal shape and less stiff mechanical characteristics around the nucleus compared to those at peripheral regions. The stiffness of the endothelial cells exposed to shear stress increased with the duration time of exposure. At 6-h exposures, the stiffness was higher at upstream side of the cell than the downstream side. However, after 24-h exposure, the stiffness was similar on both sides of the cell. These changes in the stiffness of endothelial cells when exposed to shear stress were suggested to correspond with the distribution of stress fibers in the cell. (C) 1999 Elsevier Science Ltd. All rights reserved., ELSEVIER SCI LTD
Journal of Biomechanics, 10 May 2000, [Reviewed]

Shear Stress Induced Changes in Endothelial Cell Stiffness Measured by Atomic Force Microscopy　　　　　　　　　　　　　　　
Masaaki SATO; Kazuaki NAGAYAMA; Noriyuki KATAOKA; Minoru SASAKI; and Kazuhiro HANE
Proceedings of the 1999 Summer Bioengineering Conference, 1999, [Reviewed]

〔Major achievements〕メカノセンシングにおける細胞接着・細胞骨格・核の機能，　　　　　　　　　　　　　　　
長山和亮
バイオマテリアル－生体材料－，, 20 Jan. 2020, [Invited]
Lead

〔Major achievements〕Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP signaling pathway in the remodeling of blood vessels,
Yamashiro Y; Thang BQ; Ramirez K; Shin SJ; Kohata T; Ohata S; Nguyen TA; Ohtsuki S; Nagayama K; Yanagisawa H
bioRxiv, 22 Oct. 2019

Dorsal-ventral difference in the aorta: Multiscale mechanical analysis and microarray analysis
Matsumoto Takeo; Sugita Shukei; Shirono Takahiro; Iijima Shintaro; Nagayama Kazuaki; Matsumoto Akio
Transactions of Japanese Society for Medical and Biological Engineering, 2016

〔Major achievements〕組織再生に向けた細胞のメカノトランスダクションの理解とその制御．　　　　　　　　　　　　　　　
長山和亮; 松本健郎
ファルマシア．, 01 Nov. 2015, [Reviewed]
Lead

OS18-10 Heterogeneity in the Mechanical Environment of Elastic Laminas in Porcine Thoracic Aortas(Cell and Tissue mechanics 3,OS18 Cell and tissue mechanics,BIOMECHANICS)
Matsumoto Takeo; Uno Yohei; Iijima Shintaro; Sugita Shukei; Nagayama Kazuaki
Abstracts of ATEM : International Conference on Advanced Technology in Experimental Mechanics : Asian Conference on Experimental Mechanics, 04 Oct. 2015

OS18-3 Spatiotemporal Dynamics of Actin during Adhesion Process of MC3T3-E1 Cells to Substrate(Cell and Tissue mechanics 1,OS18 Cell and tissue mechanics,BIOMECHANICS)
Wang Junfeng; Sugita Shukei; Nagayama Kazuaki; Matsumoto Takeo
Abstracts of ATEM : International Conference on Advanced Technology in Experimental Mechanics : Asian Conference on Experimental Mechanics, 04 Oct. 2015

〔Major achievements〕Nuclear-cytoskeletal Interactions in Vascular Smooth Muscle Cells: Possible Roles in the Regulation of Cell Differentiation．　　　　　　　　　　　　　　　
Nagayama K; Murakami Y; Hamaji Y; Sato Y; Matsumoto T.
Proceedings of the International Conference on Advanced Technology in Experimental Mechanics 2015．, 04 Oct. 2015, [Reviewed]
Lead

〔Major achievements〕Spatiotemporal Dynamics of Actin during Adhesion Process of MC3T3-E1 Cells to Substrate．　　　　　　　　　　　　　　　
Wang J; Sugita S; Nagayama K; Matsumoto T.
Proceedings of the International Conference on Advanced Technology in Experimental Mechanics 2015．, 04 Oct. 2015, [Reviewed]

〔Major achievements〕Heterogeneity in the Mechanical Environment of Elastic Laminas in Porcine Thoracic Aortas．　　　　　　　　　　　　　　　
Matsumoto T; Uno Y; Iijima S; Sugita S; Nagayama K.
Proceedings of the International Conference on Advanced Technology in Experimental Mechanics 2015．, 04 Oct. 2015, [Reviewed]

高度物理刺激と生体応答（3）〜力学刺激による細胞応答と応用 その１〜．
大橋俊朗; 工藤奨; 長山和亮
機械の研究．, 01 Oct. 2015, [Reviewed]
Lead

PS2-13 DYNAMICS OF ACTIN FILAMENTS DURING ADHESION PROCESS OF MC3T3-E1 CELLS TO SUBSTRATE(PS2: Poster Short Presentation II,Poster Session)
Wang Junfeng; Sugita Shukei; Nagayama Kazuaki; Matsumoto Takeo
Proceedings of the ... Asian Pacific Conference on Biomechanics : emerging science and technology in biomechanics, 16 Sep. 2015

506 The effects of the mechanical trapping of the nucleus on the cell proliferation using a micro fabricated-substrate
NAGAYAMA Kazuaki; MURAKAMI Yuki; HAMAJI Yumi; SATO Yuji; MATSUMOTO Takeo
茨城講演会講演論文集 : Ibaraki district conference, 27 Aug. 2015

J0270103 Observation of change in focal adhesion morphology during cell adhesion
WANG Junfeng; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 07 Sep. 2014

716 Development of a novel magnetic micropillar array substrate for analyzing mechanical response of cells
NAGAYAMA Kazuaki; INOUE Takuya; MATSUMOTO Takeo
茨城講演会講演論文集 : Ibaraki district conference, 04 Sep. 2014

〔Major achievements〕Analysis of the Cytoskeleton-Nucleus Mechanotransduction Pathway : Direct Force Transmission from the Actin Stress Fibers to the Nucleus　　　　　　　　　　　　　　　
長山和亮
細胞工学, 22 Aug. 2014
Lead

-最近の進歩- 細胞のバイオメカニクス：組織再生に向けたメカノトランスダクションの理解とその制御
長山和亮; 松本健郎
人工臓器, May 2014, [Reviewed]
Lead

1E14 Basic study on the measurement of deformation of endothelial glycocalyx layer exposed to laminar flow
TAKAHASHI Yutaka; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 10 Jan. 2014

1E41 Establishment of the anisotropic measurement of soft tissue elasticity with rectangular hole indentation and its application to Xenopus gastrula
NAITO Daichi; TAMURA Atsutaka; HARA Yusuke; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 10 Jan. 2014

1F11 Effects of vascular collapse during blood pressure measurement on endothelial function in the human upper arm artery
SHIMO Kenji; YAGUCHI Toshiyuki; NAGAYAMA Kazuaki; TSUKAHARA Hiromasa; MASUDA Hiroshi; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 10 Jan. 2014

1E32 Changes in the three-dimensional morphology and mechanical properties of the nucleus in aortic smooth muscle cells during serial passage culture
IWATA Makoto; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 10 Jan. 2014

A216 In situ measurement of flow mediated dilation in rabbit common carotid arteries to study the effects of their compression and occlusion
KAWAGUCHI Maki; YAGUCHI Toshiyuki; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 31 Oct. 2013

A206 Observation of change in actin filament morphology during cell adhesion in MC3T3-E1 cells
WANG Junfeng; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 31 Oct. 2013

S022021 Non- invasive measurement of pressure- diameter relationship of human brachial artery by controlling transmural pressure
YAGUCHI Toshiyuki; NAGAYAMA Kazuaki; TSUKAHARA Hiromasa; MASUDA Hiroshi; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 08 Sep. 2013

J026025 Changes in the intra- and extranuclear mechanical environment of Saos-2 osteoblastic cells during their calcification process
NAGAYAMA Kazuaki; KODAMA Fumiki; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 08 Sep. 2013

3D01 On the roles of actin stress fibers on the mechanical environment of cell nucleus
NAGAYAMA Kazuaki; YAHIRO Yuki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2013

3D08 Estimation of stress distribution in Xenopus laevis embryo from topography and stiffness distribution in its cross section
KITAMURA Hiroki; KODAIRA Ayu; HARA Yusuke; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2013

3D04 Study on the mechanism of reproducibility of stress fiber orientation in vascular smooth muscle cells : Interaction with intermediate filaments via cytoskeletal crosslinker proteins
SATO Akitoshi; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2013

1E17 Estimation of mechanical properties of epidermis and dermis by pressing a plate with a triangular hole
SUZUKI Tatsunori; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2013

A215 Direct application of mechanical stimuli to cell adhesion sites using magnetic-driven micropillars for the analysis of their tensional response
Inoue Takuya; Sugita Shukei; Nagayama Kazuaki; Matsumoto Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Oct. 2012

A211 A211 Measurement of the mechanical properties of the nucleus during bone differentiation of osteoblastic cells
Kodama Fumiki; Nagayama Kazuaki; Matsumoto Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Oct. 2012

3次元内部構造顕微鏡を用いた家兎胸大動脈壁内微細構造の観察
飯島慎太郎; 長山和亮; 中村佐紀子; 横田秀夫; 松本健郎
日本機械学会バイオフロンティア講演会講演論文集, 04 Oct. 2012

OS1104 Study on the reproducing mechanism of orientation of actin stress fibers and their internal tension levels in vascular smooth muscle cells
NAGAYAMA Kazuaki; SATO Akitoshi; YAHIRO Yuki; YANG Yunfeng; MATSUMOTO Takeo
M&M材料力学カンファレンス, 22 Sep. 2012

J028024 Study on the direct force transmission from stress fibers to nucleus : Effects of contact conditions between stress fibers and nucleus
YAMAZAKI Sho; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 09 Sep. 2012

J028016 Analysis of behavior of vascular endothelial and smooth muscle cells cultured on substrates with elasticity gradient
MATSUMOTO Takeo; NAKAGAWA Takashi; NAGAYAMA Kazuaki
Mechanical Engineering Congress, Japan, 09 Sep. 2012

J028035 Mechanism of strain waveform-dependent stress fiber reorientation in MC3T3-E1 cells induced with cyclic stretch
NAGAYAMA Kazuaki; KIMURA Yuki; MAKINO Narutaka; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 09 Sep. 2012

J028025 Estimation of stress distribution on Xenopus gastrula epithelium with laser ablation method
NAITO Daichi; SUGITA Shukei; HARA Yusuke; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 09 Sep. 2012

701 Evaluation of endothelial and smooth muscle cell functions toward ultra-early diagnosis of atherosclerosis
YAGUCHI Toshiyuki; SHIMO Kenji; KUROKAWA Takahiro; NAGAYAMA Kazuaki; TSUKAHARA Hiromasa; MASUDA Hiroshi; MATSUMOTO Takeo
東海支部総会講演会講演論文集, 15 Mar. 2012

8C42 Estimation of stress distribution in Xenopus laevis embryo with an environmental scanning electron microscope
KITAMURA Hiroki; KODAIRA Ayu; HARA Yusuke; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2012

7C34 Mechanical connection between stress fibers and the nucleus may stabilize the intranuclear DNA
NAGAYAMA Kazuaki; YAHIRO Yuki; YAMAZAKI Sho; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2012

A204 Observation of microscopic deformation in the porcine thoracic aortic walls following local laser beam ablation
UNO Yohei; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 06 Oct. 2011

A219 Direct application of mechanical strain to individual focal adhesions with magnetic micropillars and analysis of subsequent cellular response
INOUE Takuya; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 06 Oct. 2011

S022011 Study on the reproducibility of orientation of stress fibers in vascular smooth muscle cells : Interaction between intermediate filaments and stress fibers
SATO Akitoshi; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 11 Sep. 2011

S022013 Estimation of stress distribution in Xenopus laevis embryo by multidirectional measurement
KITAMURA Hiroki; ITO Kentaro; HARA Yusuke; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
Mechanical Engineering Congress, Japan, 11 Sep. 2011

血管内皮細胞の糖鎖改変による網目構造形成機構の解明に関する研究
大脇靖史; 長山和亮; 松本明郎; 松本健郎
日本機械学会年次大会講演論文集(CD-ROM), 10 Sep. 2011

9J-04 Real-time imaging of focal adhesions of HeLa cells on gel substrates
MATSUI Norihiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 07 Jan. 2011

8G-09 Effects of vascular collapse during blood pressure measurement on mechanical response of artery wall
KUROKAWA Takahiro; NAGAYAMA Kazuaki; MASUDA Hiroshi; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 07 Jan. 2011

8H-01 Study on application of mechanical stimulation to individual focal adhesions of cells using a magnetic micropillar device
NAGAYAMA Kazuaki; HAMADA Yasuhiro; INOUE Takuya; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 07 Jan. 2011

血管内皮細胞の流れ負荷に伴う変形の量子ドットを用いた局所計測の試み
大脇靖史; 長山和亮; 松本明郎; 松本健郎
バイオエンジニアリング講演会講演論文集, 07 Jan. 2011

A214 In situ observation of dynamic deformation of intracellular components induced with laser microdissection of stress fibers
YAHIRO Yuki; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 11 Nov. 2010

Mechanical force generated by leading edge mesoderm modulates collective cell polarization in axial mesoderm during Xenopus gastrulation
Yusuke Hara; Makoto Suzuki; Kazuaki Nagayama; Takeo Matsumoto; Naoto Ueno
DIFFERENTIATION, Nov. 2010

(2) Tensile Properties of Cultured Aortic Smooth Muscle Cells Obtained in a quasi-in situ Tensile Test with Thermoresponsive Gelatin
長山 和亮; 津川 昭; 松本 健郎
Journal of the Japan Society of Mechanical Engineers, 05 May 2010

0336 Observation of mineralization process and mechanical environment of osteoblast-like cells (MC3T3-E1)
Hiraoka Kenji; Nagayama Kazuaki; Matsumoto Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2010

0617 Estimation of stress distribution in Xenopus laevis embryo during development
ITO Kentaro; SHINDO Asako; NAGAYAMA Kazuaki; UENO Naoto; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2010

0615 Development of a magnetic micropillar device for applying forces to individual focal adhesions
HAMADA Yasuhiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2010

0212 Noninvasive measurement of Bayliss effect in human brachial artery
KUROKAWA Takahiro; Kato YOSHIHITO; MASUDA Hiroshi; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2010

1105 Study on the reproducibility of orientation of stress fibers and their pretension levels in vascular smooth muscle cells
NAGAYAMA Kazuaki; YAHIRO Yuki; YANG Yunfeng; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 08 Jan. 2010

A106 Pipette aspiration technique with triangular hole for measurement of depthwise distribution of elastic modulus in the soft tissue
Miyano Shinichi; Nagayama Kazuaki; Matsumoto Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 06 Nov. 2009

血管内皮細胞の細胞間接着強度測定の試み
大脇靖史; 長山和亮; 松本明郎; 松本健郎
日本機械学会バイオフロンティア講演会講演論文集, 06 Nov. 2009

Effects of glycans on mechanical behaviour of static and sheared vascular endothelial cells
大脇靖史; 長山和亮; 松本明郎; 松本健郎
日本機械学会年次大会講演論文集, 12 Sep. 2009

426 Effects of buckling of elastic lamina on pressure-diameter relationship of arteries
TAKEZAWA Kenji; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 22 Jan. 2009

313 Measurement of traction force at focal adhesions during macroscopic stretching of cells
NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 22 Jan. 2009

312 Measurement of tensile properties of single isolated aortic smooth muscle cells under controlled Ca^<2+> concentration
SAITO Shunsuke; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 22 Jan. 2009

B424 Fundamental study on the development of the magnetic micropillars for applysing mechanical stimuli to individual focal adhesions of cells
HAMADA Yasuhiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 22 Sep. 2008

B425 Analysis of mechanical response of stress fibers in aortic smooth muscle cells cultured on micropatterned substrate
YANG Yunfeng; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 22 Sep. 2008

754 Observation of microscopic deformation of porcine thoracic aortas during stretch in their thin sliced sections
SHIRONO Takahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
年次大会講演論文集 : JSME annual meeting, 02 Aug. 2008

Visualization of intracellular microstructures by 3D fluorescent optical tomography
OHARA Daisuke; ISHINO Yojiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
可視化情報学会誌. Suppl., 01 Jul. 2008

334 Contribution of actin filaments and microtubules to whole-cell mechanical properties and internal force balance of cultured aortic smooth muscle cells
NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 24 Jan. 2008

335 Basic research on the effects of substrate elasticity on the behaviour of vascular smooth muscle cells
ISHIGURO Mai; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 24 Jan. 2008

526 Estimation of stress applied to the elastic lamina and smooth muscle cells in the porcine thoracic aorta in the physiological state
MATSUMOTO Takeo; NARITA Kengo; FUKUNAGA Akihisa; NAGAYAMA Kazuaki
バイオエンジニアリング講演会講演論文集, 24 Jan. 2008

425 Real-time observation of immature bone tissue in culture under mechanical stimulation
ICHIKAWA Katsuhisa; NAGAYAMA Kazuaki; MATSUMOTO Takeo
第20回バイオエンジニアリング講演会公演論文集, 2008, 2008

EFFECTS OF ACTIN FILAMENTS AND MICROTUBULES ON QUASI-IN SITU TENSILE PROPERTIES AND INTRACELLULAR FORCE BALANCE OF CULTURED AORTIC SMOOTH MUSCLE CELLS(1A2 Micro & Nano Biomechanics II)
Nagayama Kazuaki; Matsumoto Takeo
Proceedings of the ... Asian Pacific Conference on Biomechanics : emerging science and technology in biomechanics, 05 Nov. 2007

A110 Measurement of the effects of smooth muscle contraction on radial distribution of intramural strain in the blood vessel
OHOKA Makoto; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 05 Oct. 2007

S-30. 大動脈壁内平滑筋細胞のバイオメカニクス : 新鮮単離細胞の力学特性計測と血管壁内力学環境の推定(血管平滑筋研究の新展開, 第49回日本平滑筋学会総会)
松本 健郎; 成田 健吾; 長山 和亮
日本平滑筋学会雑誌, 26 Jun. 2007

2401 Development of a novel scanning micro-indentation tester with real-time observation of measuring point
OIWA Mikio; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Conference on Information, Intelligence and Precision Equipment : IIP, 19 Mar. 2007

606 Estimation of residual stress in the smooth muscle cells in porcine thoracic aortic walls under macroscopically no load condition
NARITA Kengo; FUKUNAGA Akihisa; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

412 Development of a Novel Observation Method for 3D Morphology of Cells Using Distributing Back Projection Method and Its Application to C. elegans Eggs
OGAWA Masayuki; HIRAKI Hideaki; ISHINO Yojiro; WAKE Fuminori; NAGAYAMA Kazuaki; KOHARA Yuji; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

405 Three-dimensional morphological analysis of mechanical response of MC3T3-E1 osteoblast-like cells cultured in collagen gel
NAGAYAMA Kazuaki; SUGIYAMA Takahiko; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

439 Effects of Three-Dimensional Culture and Mechanical Stimulation on Contractile Protein Expression in Freshly Isolated Vascular Smooth Muscle Cells
MORISHIMA Naoki; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

438 Effects of cyclic stretch waveform on alignment of osteoblast-like cells in two-dimensional culture
INOUE Ryo; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

224 Basic research on the development of flute-blowing apparatus and tone analysis
MATSUMOTO Takeo; ITO Ikuo; TAKEUCHI Risa; NAGAYAMA Kazuaki
バイオエンジニアリング講演会講演論文集, 06 Jan. 2007

A210 Biaxial tensile properties of the wrinkled skin of UV-irradiated mice
MORI Mako; IKUTA Naoko; NAGAYAMA Kazuaki; AMANO Satoshi; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 10 Nov. 2006

121 Measurement of traction force of cultured smooth muscle cells on a substrate coated with thermoresponsive gelatin
TSUGAWA Akira; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 12 Jan. 2006

119 Effects of inhibition of tubulin polymerization and depolymerization on tensile properties and cell shortening dunng detachment of cultured aortic smooth muscle cells
NAGAYAMA Kazuaki; TSUGAWA Akira; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 12 Jan. 2006

204 Microscopic measurement of tensile and shear moduli of the elastic layer and smooth muscle layer of the porcine thoracic aortic wall
TANIGUCHI Masahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 12 Jan. 2006

A106 Basic research of the response of mouse bone marrow cells to cyclic stretch : Relation between morphology and protein expression
ATSUMI Yoshinori; ISHIGURO Mai; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 08 Nov. 2005

A105 Response of MC3T3-E1 osteoblast like cells to cyclic stretch
INOUE Ryo; SUGIYAMA Takahiko; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 08 Nov. 2005

血管壁内残留応力のマルチスケール解析
松本 健郎; 谷口 雅洋; 福永 晃久; 成田 健吾; 長山 和亮
日本バイオレオロジー学会年会抄録集, 30 Jun. 2005

Shear modulus of the porcine thoracic aortic wall and its relation to histology
TANIGUCHI Masahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Nov. 2004

Effect of contraction on mechanical anisotropy of freshly-isolated vascular smooth muscle cells
NAKAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Nov. 2004

Morphological analysis of mouse bone marrow cells exposed to cyclic stretch
ATSUMI Yoshinori; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Nov. 2004

Development of a novel cell rotation device and its application to 3D observation of cell morphology
WAKE Fuminori; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 04 Nov. 2004

Circumferential differences of smooth muscle contraction in rabbit descending thoracic aorta
SHIRONO Takahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
バイオエンジニアリング講演会講演論文集, 21 Jan. 2004

Measurement and analysis of residual stress and strain in the porcine thoracic aorta from a microscopic viewpoint
FURUKAWA Takao; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 17 Sep. 2003

Response of cultured vascular endothelial cells on microgrooved silicone sheet to cyclic stretch
YANAGIHARA Shinichiro; NAKAGAKI Masashi; NAGAYAMA Kazuaki; MATSUMOTO Takeo
Proceedings of the ... JSME Conference on Frontiers in Bioengineering, 17 Sep. 2003

Effect of cell components on single isolated vascular smooth muscle cell
NAGANO Yujiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo; SATO Masaaki
講演論文集, 15 Mar. 2003

The Development of Cell Rotation Systems (CRS) and Fundamental Study of 3D Observations of Cell Structure
TAJIMA Hideki; NAGAYAMA Kazuaki; Ito Kazunori; MATSUMOTO Takeo; SATO Masaaki
講演論文集, 15 Mar. 2003

Experimental analysis of microscopic residual stress and strain in the arterial wall
FURUKAWA Takao; NAGAYAMA Kazuaki; MATSUMOTO Takeo
東海支部総会講演会講演論文集, 01 Mar. 2003

The influence of intracellular structure on mechanical properties of artery smooth muscle cells
NAGAYAMA Kazuaki; NAGANO Yujiro; SATO Masaaki; MATSUMOTO Takeo
東海支部総会講演会講演論文集, 01 Mar. 2003

Measurement of difference of smooth muscle contraction in circumferential sections at rabbit's descending thoracic aorta (DTA)
SHIRONO Takahiro; NAGAYAMA Kazuaki; MATSUMOTO Takeo
東海支部地区講演会講演論文集, 2003

Effect of ambient temperature and freeze storage on the biaxial tensile properties of aortic wall
IKUTA Naoko; NAGAYAMA Kazuaki; MATSUMOTO Takeo
東海支部地区講演会講演論文集, 2003

Vascular Engineering, New Prospects of Vascular Medicine and Biology with a Multidiscipline Approach．　　　　　　　　　　　　　　　
Takeo Matsumoto; Shukei Sugita; Kazuaki Nagayama., Contributor
Springer．, 20 Jan. 2016
9784431548003

On the roles of actin stress fibers on the mechanical environment of nucleus in vascular smooth muscle cells, Recent Advances in Mechanobiology．　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA; Yuki YAHIRO; Takeo MATSUMOTO, Joint work
Shanghai Scientific and Technological Literature Publishing House (Editor-in-Chief: Shu Chien, Shi Yongde, and Masahiro Sokabe)．, 01 May 2012

Effects of cytoskeletal structures on elastic and viscoelastic properities of cells in soft tissues, Biomechanics at Micro- and Nanoscale Levels, Volume IV．　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Kazuaki NAGAYAMA,Hiroshi MIYAZAKI,and Yoshihiro UJIHARA., Joint work
World Scientific, Singapore．, 20 Apr. 2007

Measurement of Mechanical Properties of Cells Considering Their Intracellular Microstructures, Biomechanics at Micro- and Nanoscale Levels, Volume II．　　　　　　　　　　　　　　　
Takeo MATSUMOTO and Kazuaki NAGAYAMA., Joint work
World Scientific, Singapore．, 15 Oct. 2006

Microscopic Analysis of Residual Stress and Strain in the Aortic Media Considering Anisotropy of Smooth Muscle Layer, Holzapfel GA, Ogden RW, eds, Mechanics of Biological Tissue．　　　　　　　　　　　　　　　
Takeo MATSUMOTO; Takao FURUKAWA; and Kazuaki NAGAYAMA., Joint work
Springer-Verlag．, 20 Sep. 2006

マイクロ矩形溝基板を用いた細胞核拘束による血管平滑筋分化誘導 〜生体材料製微細溝基板への展開〜　　　　　　　　　　　　　　　
長山和亮; 新井翔真; 綿谷直樹
日本機械学会東北支部 第60期総会・講演会, 17 Mar. 2025
20250317, 20250317

Study on the Effect of Cell Trapping by Biomaterial Micro Rectangular Groove Substrates on Vascular Smooth Muscle Differentiation　　　　　　　　　　　　　　　
新井翔真; 長山和亮
日本機械学会関東学生会第64回学生員卒業研究発表講演会, 03 Mar. 2025

Study on the Effects of Microgravity on the Mechanical Structure of Cell and Nuclei　　　　　　　　　　　　　　　
廣木秀翔; 長山和亮
日本機械学会関東学生会第64回学生員卒業研究発表講演会, 03 Mar. 2025

Analysis of structural recovery mechanism of actin stress fibers using laser nanosurgery　　　　　　　　　　　　　　　
弓野奎斗; 王軍鋒; 松本健郎; 長山和亮
日本機械学会 第35回バイオフロンティア講演会,, 14 Dec. 2024
20241214, 20241215

Effects of microgravity on cellular and nuclear mechanical structure　　　　　　　　　　　　　　　
池田佳津希; 廣木秀翔; 中村麻子; 長山和亮
日本機械学会 第35回バイオフロンティア講演会, 14 Dec. 2024
20241214, 20241215

Atomic force microscopy estimation of mechanical properties of tunneling nanotubes in cancer cells.　　　　　　　　　　　　　　　
Rintaro Ota; Kazuaki Nagayama
生体医工学シンポジウム2024, 13 Sep. 2024
20240912, 20240914

Experimental study of the mechanical environment of the nucleus of iPS cells derived from claviculo-cranial dysplasia (CCD).　　　　　　　　　　　　　　　
長山和亮; 齋藤暁子; 東俊文
日本機械学会 2024年度年次大会, 10 Sep. 2024
20240909, 20240911

Measurement of Responses in Tensile Stimulation for Biocompatible Force Sensors Using FRET Function Introduced Cells　　　　　　　　　　　　　　　
岡﨑駿斗; 北口哲也; 長山和亮; 上杉薫
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Analysis of self-recovery mechanism after cytoskeletal disruption using laser nanosurgery　　　　　　　　　　　　　　　
弓野奎斗; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Analysis of the effect of deformation rate on mechanical damage and self-repair mechanisms of cell skeletal components　　　　　　　　　　　　　　　
佐野真太; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Aligned vascular smooth muscle cell tissue formation using microgroove substrates and intracellular structure analysis ~Effect of rectangular microgroove substrates derived from biomaterials on cells~　　　　　　　　　　　　　　　
山崎泰成; 上杉薫; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Analysis for mechanical property of actin stress fibers regulating cell and tissue mechanical structure　　　　　　　　　　　　　　　
神邊千穂; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

The investigation of the mechanical properties and roles of nanofibers participated in intercellular communication in cancer cells　　　　　　　　　　　　　　　
太田倫汰郎; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Development of Friction Force Measurement System to Elucidate the Mechanism of Anti-contamination Function of Ascidian's Surface Nanostructures　　　　　　　　　　　　　　　
大内椋太; 広瀬裕一; 長山和亮; 上杉薫
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

Cell nucleus segmentation and cell type classification from phase-contrast microscope images enabled by machine learning　　　　　　　　　　　　　　　
武田翔太郎; 竹田晃人; 長山和亮
日本機械学会 2024年度茨城講演会, 30 Aug. 2024

動脈ラメラ構造を模擬した微細溝凹部細胞培養系による血管平滑筋分化誘導:細胞核の力学的拘束が血管平滑筋分化を促進させる　　　　　　　　　　　　　　　
長山和亮; 綿谷直樹
第76回 日本細胞生物学会大会, 19 Jul. 2024
20240717, 20240719

分子ロボットへの応用を目的に膜組成を変更したリポソームのマイクロピペット吸引試験による機械的特性評価　　　　　　　　　　　　　　　
清田匠; 豊田太郎; 長山和亮; 上杉薫
ロボティクス・メカトロニクス 講演会, 29 May 2024
20240529, 20240601

力学的バイスタンダー効果による細胞内DNA損傷の発生メカニズム　　　　　　　　　　　　　　　
長山和亮; 廣岡祐仁; 中村麻子
第63回日本生体医工学会大会, 24 May 2024
20240523, 20240525

生物表面のナノ構造による液中での防汚機能メカニズム解明を目的とした摩擦力評価　　　　　　　　　　　　　　　
大内椋太; 広瀬裕; 長山和亮; 上杉薫
日本機械学会 第36回バイオエンジニアリング講演会, 12 May 2024
20240511, 20240512

がん細胞のコミュニケーションを担う トンネルナノチューブ様構造の力学特性評価　　　　　　　　　　　　　　　
太田倫汰郎; 長山和亮
日本機械学会 第36回バイオエンジニアリング講演会, 12 May 2024
20240511, 20240512

力学刺激による細胞骨格の強化と細胞の配向変化が創傷治癒運動に与える影響　　　　　　　　　　　　　　　
池田佳津希; 長山和亮
日本機械学会 第36回バイオエンジニアリング講演会, 12 May 2024
20240511, 20240512

分子ロボットのためのしなやかな筐体開発に向けたリポソームの機械的特性評価　　　　　　　　　　　　　　　
上杉薫; 清田匠; 豊田太郎; 長山和亮
日本機械学会 第36回バイオエンジニアリング講演会, 11 May 2024
20240511, 20240512

細胞構造を維持するアクチンストレスファイバの再生メカニズム解析　　　　　　　　　　　　　　　
神邊千穂; 長山和亮
日本機械学会 第36回バイオエンジニアリング講演会, 11 May 2024
20240511, 20240512

局所的圧縮刺激培養系の構築と細胞のDNA損傷解析（力学的刺激のバイスタンダー効果による細胞癌化可能性）,　　　　　　　　　　　　　　　
長山和亮,廣岡祐仁,中村麻子
日本機械学会東北支部第59期総会・講演会,, 15 Mar. 2024, 日本機械学会
20240313, 20240313

Cell nucleus segmentation and cell type classification from stain-free phase-contrast images enabled by machine learning,　　　　　　　　　　　　　　　
武田翔太郎,竹田晃人,長山和亮
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

Effects of changes in intracellular structure and cellular organization induced by mechanical stimulation on wound healing process,　　　　　　　　　　　　　　　
池田佳津希,長山和亮
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

Evaluation for Frictional Force to Elucidate Anti-fouling Function of Nanostructure of Biplogical Surfaces,　　　　　　　　　　　　　　　
大内椋太,広瀬裕一,長山和亮,上杉薫
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

Development of force sensor used cells introduced with fluorescence resonance energy transfer (FRET),　　　　　　　　　　　　　　　
岡崎駿斗,北口哲也,長山和亮,上杉薫
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

The investigation of the mechanical properties of membrane nanotubes participated in intercellular communication in cancer cells,　　　　　　　　　　　　　　　
太田倫汰郎,長山和亮
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

Study on the repair ability of actin stress fibers regulating cell mechanical structures,　　　　　　　　　　　　　　　
神邊千穂,長山和亮
日本機械学会関東学生会第63回学生員卒業研究発表講演会,, 13 Mar. 2024, 日本機械学会
20240313, 20240313

ストレスファイバーのプリストレインを考慮した培養血管平滑筋細胞の数値モデリング,　　　　　　　　　　　　　　　
田邉康裕,長山和亮,田村篤敬
日本機械学会中国四国支部 第62期総会・講演会,, 07 Mar. 2024, 日本機械学会
20240307, 20240307

基質表面の微小ジオメトリによる細胞機能制御の試み,　　　　　　　　　　　　　　　
長山和亮
精密工学会「微細加工と表面機能専門委員会」第３回セミナー,, 22 Jan. 2024, 精密工学会
20240122, 20240122

分子ロボット開発を目的としたリポソームの機械的特性評価と膜組成の提案,　　　　　　　　　　　　　　　
清田 匠,豊田 太郎,長山 和亮,上杉 薫
日本機械学会 第34回バイオフロンティア講演会,, 17 Dec. 2023, 日本機械学会
20231216, 20231217

2軸微小力センサ搭載摩擦力測定システムによる生物体表を模倣したナノ構造の摩擦力評価,　　　　　　　　　　　　　　　
大内椋太,広瀬裕一,長山和亮,上杉薫
日本機械学会 第34回バイオフロンティア講演会,, 17 Dec. 2023, 日本機械学会
20231216, 20231217

局所的圧縮で誘発される皮膚線維芽細胞のDNA損傷メカニズム（力学的バイスタンダー効果による細胞がん化の可能性）,　　　　　　　　　　　　　　　
廣岡祐仁,中村麻子,長山和亮
日本機械学会 第34回バイオフロンティア講演会,, 16 Dec. 2023, 日本機械学会
20231216, 20231217

局所的圧縮による皮膚線維芽細胞の組織的運動とDNA損傷との関わり～力学的バイスタンダー効果の可能性～,　　　　　　　　　　　　　　　
廣岡祐仁,中村麻子,長山和亮
日本生体医工学会関東支部若手研究者発表会2023,, 09 Dec. 2023, 日本生体医工学会
20231209, 20231209

がん細胞間の情報伝達を担うトンネルナノチューブ様構造の力学特性評価,　　　　　　　　　　　　　　　
太田倫汰郎 ,長山和亮
日本生体医工学会関東支部若手研究者発表会2023,, 09 Dec. 2023, 日本生体医工学会
20231209, 20231209

細胞構造を支えるアクチンストレスファイバの収縮・再生メカニズム解析,　　　　　　　　　　　　　　　
神邊千穂,弓野奎斗,長山和亮
日本生体医工学会関東支部若手研究者発表会2023,, 09 Dec. 2023, 日本生体医工学会
20231209, 20231209

〔Major achievements〕細胞バイオメカニクス（機械工学で細胞の仕組みを解き明かす）,　　　　　　　　　　　　　　　
長山和亮,
日本機械学会中国四国支部 特別講演会「令和5年度 鳥取地区講演会」,, 20 Oct. 2023, 日本機械学会, [Invited]
20231020, 20231020

〔Major achievements〕細胞バイオメカニクス:機械工学技術を駆使した細胞分析･操作への展開,　　　　　　　　　　　　　　　
長山和亮,
日本機械学会 M&M2023 材料力学カンファレンス,, 28 Sep. 2023, 日本機械学会, [Invited]
20230927, 20230929

Analysis of cell mechanical adaptation mechanism using stretching apparatus for atomic force microscope,　　　　　　　　　　　　　　　
佐野 真太,長山 和亮
日本機械学会 M&M2023 材料力学カンファレンス, 28 Sep. 2023, 日本機械学会
20230927, 20230929

Analysis for repair mechanism of cells following laser dissection of actin stress fibers,　　　　　　　　　　　　　　　
弓野奎斗,長山和亮
日本機械学会 M&M2023 材料力学カンファレンス, 28 Sep. 2023, 日本機械学会
20230927, 20230929

Evaluation of Mechanical Properties of Liposomes with Different Membrane Compositions by the Micropipette aspiration method,　　　　　　　　　　　　　　　
清田匠,豊田太郎,長山和亮,上杉薫
日本機械学会 M&M2023 材料力学カンファレンス, 28 Sep. 2023, 日本機械学会
20230927, 20230929

Construction of the micromechanical environment of arterial tissue by micro-grooved cell culture substrates and inducement of vascular smooth muscle differentiation,　　　　　　　　　　　　　　　
長山 和亮,綿谷 直樹,山崎 泰成
日本機械学会2023年度年次大会,, 06 Sep. 2023, 日本機械学会
20230903, 20230906

Characterization of Mechanical Properties of Liposome using a Microfluidic Device for Molecular Robotics Applications,　　　　　　　　　　　　　　　
上杉 薫,柏木 悠里,豊田 太郎,長山 和亮
日本機械学会2023年度年次大会,, 06 Sep. 2023, 日本機械学会
20230903, 20230906

〔Major achievements〕BIOMECHANICAL ANALYSIS FOR A SELF-REPAIR MECHANISM OF ACTIN STRESS FIBERS,　　　　　　　　　　　　　　　
Kazuaki Nagayama
6th Japan-Switzerland Workshop on Biomechanics (JSB2023),, 30 Aug. 2023, The 6th Japan-Switzerland Workshop on Biomechanics (JSB2023), [Invited]
20230829, 20230901

Effects of local compression on DNA damage of skin fibroblasts, ~Mechanical bystander effects inducing cancer generation ~,　　　　　　　　　　　　　　　
廣岡 祐仁,長山 和亮
日本機械学会 2023年度茨城講演会, 18 Aug. 2023, 日本機械学会
20230818, 20230818

Analysis of partial damage and repair mechanistic of the cytoskeleton by deformation rate using atomic force microscopy,　　　　　　　　　　　　　　　
佐野 真太,長山 和亮
日本機械学会 2023年度茨城講演会, 18 Aug. 2023, 日本機械学会
20230818, 20230818

Analysis for micro wound and repair mechanism of cells using laser ablation method,　　　　　　　　　　　　　　　
弓野 奎斗,長山 和亮
日本機械学会 2023年度茨城講演会, 18 Aug. 2023, 日本機械学会
20230818, 20230818

Analysis for cell responses in the aligned vascular smooth muscle cell tissue under cyclic stretch stimulation,　　　　　　　　　　　　　　　
山崎 泰成,上杉 薫,長山 和亮
日本機械学会 2023年度茨城講演会, 18 Aug. 2023, 日本機械学会
20230818, 20230818

Evaluating Mechanical Properties of Liposomes for Molecular Robot Development, - Evaluation of Liposomes with Different Membrane Compositions -,　　　　　　　　　　　　　　　
清田 匠,豊田 太郎,長山 和亮,上杉 薫
日本機械学会 2023年度茨城講演会, 18 Aug. 2023, 日本機械学会
20230818, 20230818

鎖骨頭蓋骨異形成症とラミノパチー骨病変の病態は類似する,　　　　　　　　　　　　　　　
齋藤暁子,長山和亮,小野寺晶子,間 奈津子,岡田 寛之,北條 宏徳,大庭伸介,加藤茂明,東俊文
第41回日本骨代謝学会学術集会,, 27 Jul. 2023, 日本骨代謝学会,
20230727, 20230729

Biomechanical analysis for repair mechanism of actin stress fibers using a laser ablation method,　　　　　　　　　　　　　　　
長山和亮,
第75回日本細胞生物学会,, 28 Jun. 2023, 日本細胞生物学会,
20230628, 20230630

Runx2 新規機能。Runx2 は LINC 構築と核アクチンキャップ構造構築を通じ核ラミナ - クロマチン相互関係を制御する,　　　　　　　　　　　　　　　
東 俊文; 長山和亮; 小野寺晶子; 間 奈津子; 岡田寛之; 北條宏徳; 大庭伸介; 齋藤暁子
第75回日本細胞生物学会,, 28 Jun. 2023, 日本細胞生物学会,
20230628, 20230630

Cell nucleus tracking in stain-free phase contrast images enabled by machine learning, and its application for cell diagnosis,　　　　　　　　　　　　　　　
Miku OHASHI; Kazuaki NAGAYAMA
日本機械学会 第35回バイオエンジニアリング講演会, 03 Jun. 2023, 日本機械学会
20230603, 20230604

配列化血管平滑筋細胞組織への繰返引張負荷およびリアルタイム応答観察,　　　　　　　　　　　　　　　
Taisei YAMAZAKI; Kazuaki NAGAYAMA
日本機械学会 第35回バイオエンジニアリング講演会, 03 Jun. 2023, 日本機械学会
20230603, 20230604

原子間力顕微鏡組込型の引張試験機を用いた細胞損傷の解析, 〜 引張速度による細胞損傷発生の違い 〜,　　　　　　　　　　　　　　　
Shinta SANO; Kazuaki NAGAYAMA
日本機械学会 第35回バイオエンジニアリング講演会, 03 Jun. 2023, 日本機械学会
20230603, 20230604

アクチンストレスファイバ切断後の損傷回復メカニズム解析,　　　　　　　　　　　　　　　
Keito YUMINO; Kazuaki NAGAYAMA
日本機械学会 第35回バイオエンジニアリング講演会, 03 Jun. 2023, 日本機械学会
20230603, 20230604

Development of vascular micro-mechanical environment using micro-grooved substrates and its application to improve vascular smooth muscle differentiation,　　　　　　　　　　　　　　　
長山和亮,
第62回日本生体医工学会大会,, 18 May 2023, 日本生体医工学会大会, [Invited]
20230518, 20230520

Development of cell culture and observation system considering mechanical environment of vascular wall and analysis of cell response,　　　　　　　　　　　　　　　
山崎泰成,長山和亮
日本機械学会関東学生会第62回学生員卒業研究発表講演会，, 16 Mar. 2023, 日本機械学会
20230316, 20230316

Development of stretching apparatus for atomic force microscope and analysis of cell mechanical adaptation mechanism,　　　　　　　　　　　　　　　
佐野真太,長山和亮
日本機械学会関東学生会第62回学生員卒業研究発表講演会，, 16 Mar. 2023, 日本機械学会
20230316, 20230316

Analysis for retraction and repair mechanism of actin stress fibers by laser dissection method,　　　　　　　　　　　　　　　
弓野奎斗,長山和亮
日本機械学会関東学生会第62回学生員卒業研究発表講演会，, 16 Mar. 2023, 日本機械学会
20230316, 20230316

Development of vascular micro-mechanical environment using micro-grooved substrates and its application to improve cellular contractile functions,　　　　　　　　　　　　　　　
長山 和亮,綿谷 直樹
2023年度精密工学会春季大会,, 16 Mar. 2023, 精密工学会
20230314, 20230316

Biomechanical analysis for cellular wound repair mechanism using a laser ablation method,　　　　　　　　　　　　　　　
長山 和亮
2023年度精密工学会春季大会,, 16 Mar. 2023, 精密工学会
20230314, 20230316

マイクロ溝基板を用いた細胞配列化制御と低・無血清培養による血管平滑筋分化誘導,　　　　　　　　　　　　　　　
綿谷 直樹,長山 和亮
日本生体医工学会関東支部若手研究者発表会2022,, 10 Dec. 2022, 日本生体医工学会
20221210, 20221210

機械学習を用いた無染色位相差顕微鏡画像からの細胞核抽出と評価,　　　　　　　　　　　　　　　
大橋 未来,長山 和亮
日本生体医工学会関東支部若手研究者発表会2022,, 10 Dec. 2022, 日本生体医工学会
20221210, 20221210

原子間力顕微鏡組込型の引張試験機の開発と力に対する細胞の張力変化の解析,　　　　　　　　　　　　　　　
佐野 真太,長山 和亮
日本生体医工学会関東支部若手研究者発表会2022,, 10 Dec. 2022, 日本生体医工学会
20221210, 20221210

〔Major achievements〕Biomechanical Approaches for Investigating the Roles of Actin-Nucleus Interactions in Vascular Cell Functions,　　　　　　　　　　　　　　　
Nagayama K
4th International Symposium on Nanoarchitectonics for Mechanobiology (Mechano-X BIO&CHEM 2022),, 16 Nov. 2022, 4th International Symposium on Nanoarchitectonics for Mechanobiology (Mechano-X BIO&CHEM 2022),, [Invited]
20221116, 20221116

The effects of mechanical trapping of cells into the concave micro-grooves on the cell nucleus and differentiation of the vascular smooth muscle cells,　　　　　　　　　　　　　　　
綿谷 直樹,上杉 薫,長山 和亮
日本機械学会2022年度年次大会,, 12 Sep. 2022, 日本機械学会
20220911, 20220914

Evaluating Mechanical Properties of Liposomes with Optical Mechanical Properties for Molecular Robot Development,　　　　　　　　　　　　　　　
清田 匠,豊田 太郎,長山 和亮,上杉 薫
日本機械学会2022年度年次大会,, 12 Sep. 2022, 日本機械学会
20220911, 20220914

The effect of mechanical stress on cellular DNA damage -Cell density-dependent DNA damage regulation-,　　　　　　　　　　　　　　　
廣岡 祐仁,上杉 薫,長山 和亮
日本機械学会 2022年度茨城講演会, 19 Aug. 2022, 日本機械学会
20220819, 20220819

Regulation of cell morphology using microgroove substrates and analysis of three-dimensional intercellular structures,　　　　　　　　　　　　　　　
綿谷 直樹,上杉 薫,長山 和亮
日本機械学会 2022年度茨城講演会, 19 Aug. 2022, 日本機械学会
20220819, 20220819

Evaluating Mechanical Properties of Liposomes for Development of Molecular Robots -Improvement for Stability of Micropipette Aspiration Method-,　　　　　　　　　　　　　　　
清田 匠,豊田 太郎,長山 和亮,上杉 薫
日本機械学会 2022年度茨城講演会, 19 Aug. 2022, 日本機械学会
20220819, 20220819

〔Major achievements〕Observation of nucleus-actin dynamics invascular smooth muscle cells during cyclic stretching,
Nagayama K
9th World Congress of Biomechanics (WCB2022),, 13 Jul. 2022, 9th World Congress of Biomechanics (WCB2022),
20220710, 20220714

〔Major achievements〕The Roles of Nuclear-cytoskeletal Interactions in Vascular Smooth Muscle Cell Differentiation,
Nagayama K
9th World Congress of Biomechanics (WCB2022),, 12 Jul. 2022, 9th World Congress of Biomechanics (WCB2022),
20220710, 20220714

分子ロボット開発を目的とするリポソームの機械的特性評価法の確立～マイクロピペット吸引法の適用～　　　　　　　　　　　　　　　
柏木悠里,豊田太郎,長山和亮,上杉薫
日本機械学会ロボティクス・メカトロニクス 講演会 2023，, 28 Jun. 2023, 日本機械学会
20220628, 20220630

〔Major achievements〕Roles of actin cytoskeleton for cellular mechanical responses and wound repairing,　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA
日本機械学会 第34回バイオエンジニアリング講演会, 25 Jun. 2022, 日本機械学会, [Invited]
20220625, 20220626

Basic study on the regulation of cell orientation and multilayered cell sheets,　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA
日本機械学会 第34回バイオエンジニアリング講演会, 25 Jun. 2022, 日本機械学会
20220625, 20220626

細胞密集状態が細胞の紫外線由来DNA損傷に与える影響～細胞種による応答比較～,　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA
日本機械学会 第34回バイオエンジニアリング講演会, 25 Jun. 2022, 日本機械学会
20220625, 20220626

分子ロボット開発を目的とするリポソームの機械的特性評価法の確立～マイクロピペット吸引法の適用～　　　　　　　　　　　　　　　
清田匠,長山和亮,豊田太郎,上杉薫
日本機械学会ロボティクス・メカトロニクス 講演会 2022，, 02 Jun. 2022, 日本機械学会
20220601, 20220604

骨芽細胞Runx2は核膜ラミナタンパク質発現調節を通じて核形態および骨芽細胞分化を制御する　　　　　　　　　　　　　　　
東俊文; 齋藤暁子; 中村貴; 間奈津子; 小野寺晶; 岡田 寛之; 北條 宏徳; 長山 和亮
第21回日本再生医療学会総会, 18 Mar. 2022, 日本再生医療学会
20220317, 20220319

細胞位相差画像の時間差分における特徴量抽出と細胞分裂タイミングの予測　　　　　　　　　　　　　　　
段木穂高; 竹田晃人; 長山和亮
日本物理学会第77回年次大会, 16 Mar. 2022, 日本物理学会
20220315, 20220318

細胞配列化と繰返引張刺激による血管平滑筋細胞の分化誘導への試み　　　　　　　　　　　　　　　
綿谷直樹,上杉薫,長山和亮
日本機械学会関東支部 第28期総会・講演会，, 14 Mar. 2022, 日本機械学会
20220314, 20220315

位相差顕微鏡画像の特徴量抽出によるHeLa細胞の分裂周期の予測　　　　　　　　　　　　　　　
段木穂高,竹田晃人,長山和亮
日本機械学会関東支部 第28期総会・講演会，, 14 Mar. 2022, 日本機械学会
20220314, 20220315

細胞間の力学的相互作用が細胞の紫外線耐性に与える影響～細胞密度および細胞種の違いによる応答変化～　　　　　　　　　　　　　　　
廣岡祐仁,上杉薫,長山 和亮
日本機械学会関東学生会第61回学生員卒業研究発表講演会，, 14 Mar. 2022, 日本機械学会
20220314, 20220314

配向を制御した重層化細胞組織の形成に関する研究　　　　　　　　　　　　　　　
中澤未来,上杉薫,長山和亮
日本機械学会関東学生会第61回学生員卒業研究発表講演会，, 14 Mar. 2022, 日本機械学会
20220314, 20220314

分子ロボット開発を目的とするリポソームの機械的特性評価法の確立～マイクロピペット吸引法の適用～　　　　　　　　　　　　　　　
清田匠,上杉薫,長山和亮
日本機械学会関東学生会第61回学生員卒業研究発表講演会，, 14 Mar. 2022, 日本機械学会
20220314, 20220314

細胞核の変形がDNAの紫外線耐性を向上させるメカニズムに関する研究　　　　　　　　　　　　　　　
三浦光騎,長山和亮
日本機械学会 第 32 回バイオフロンティア講演会，, 12 Jan. 2022, 日本機械学会
20220112, 20220113

Cell type-difference of mechanical properties and ability in substrate mechanosensing,　　　　　　　　　　　　　　　
Nagayama K; Hanzawa T; Obata S
11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021),, 02 Dec. 2021, 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),
20211202, 20211205

Nipple-Array Inhibits Adhesion Force in the Water: Clarifying Functional Nano-Scale Structures of Ascidians Surface Body,　　　　　　　　　　　　　　　
Uesugi K; Nagayama K; Hirose E
11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021),, 02 Dec. 2021, 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),
20211202, 20211205

Analysis of the changes in nucleus-cytoskeleton connection in vascular smooth muscle cells under cyclic stretch stimulation,　　　　　　　　　　　　　　　
Ikeda K; Uesugi K; Nagayama K
11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021),, 02 Dec. 2021, 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),
20211202, 20211205

Facilitation for the vascular smooth muscle cell differentiation by arranging cell orientation and cyclic stretch stimulation,　　　　　　　　　　　　　　　
Wataya N; Uesugi K; Nagayama K
11th Asian-Pacific Conference on Biomechanics (AP Biomech 2021),, 02 Dec. 2021, 11th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),
20211202, 20211205

部分空間法を用いた癌細胞分裂開始からの経過時間予測　　　　　　　　　　　　　　　
段木穂高; 竹田晃人; 長山和亮
日本物理学会2021年度秋季大会, 12 Sep. 2021, 日本物理学会
20210912, 20210915

〔Major achievements〕Changes in the tensional dynamics of actin stress fibers in vascular smooth muscle cells through cell de-differentiation and cell senescence　　　　　　　　　　　　　　　
長山 和亮,菅野 隼太,野上 謙三
日本機械学会2021年度年次大会,, 07 Sep. 2021, 日本機械学会
20210906, 20210908

〔Major achievements〕Evaluation for Mechanical and Adhesion Properties of Single Cells by Using Micro-tensile Testing System Working Under the Microscope -Mechanical properties of HeLa cells which was inhibited polymerization of microtubules-　　　　　　　　　　　　　　　
上杉 薫,小幡 祥太,長山 和亮
日本機械学会2021年度年次大会,, 07 Sep. 2021, 日本機械学会
20210906, 20210908

Evaluation of Adhesion Force of Ascidian Surface to Clarifying the Function of Nipple Array　　　　　　　　　　　　　　　
上杉 薫,長山 和亮,広瀬 裕一
日本機械学会2021年度年次大会,, 06 Sep. 2021, 日本機械学会
20210906, 20210908

Establishment of a cell culture experimental system in consideration of the mechanical and biochemical environment of the vascular wall　　　　　　　　　　　　　　　
綿谷 直樹,上杉 薫,長山 和亮
日本機械学会 2021年度茨城講演会, 19 Aug. 2021, 日本機械学会
20210819, 20210819

Development of a stretch stimulation system on microscope for,analyzing the mechanical responses of cells　　　　　　　　　　　　　　　
池田 圭吾,上杉 薫,長山 和亮
日本機械学会 2021年度茨城講演会, 19 Aug. 2021, 日本機械学会
20210819, 20210819

Macroscopic and microscopic analysis of the mechanical properties and adhesion force of cells using a single cell tensile test and atomic force microscopy,　　　　　　　　　　　　　　　
Nagayama K
the 3M conference (Materials, Mimics, and Microfluidics: Engineering Tools for Mechanobiology), 21 Jul. 2021, the Mechanobiology Institute/National University of Singapore.
20210721, 20210723

〔Major achievements〕On the role of the nuclear-cytoskeletal interactions in the regulation of cell function　　　　　　　　　　　　　　　
Kazuaki NAGAYAMA
日本機械学会 第33回バイオエンジニアリング講演会, 25 Jun. 2021, 日本機械学会, [Invited]
20210625, 20210626

〔Major achievements〕微細溝コラーゲン基質上で配列化培養した血管平滑筋細胞への繰返伸展刺激負荷　　　　　　　　　　　　　　　
綿谷 直樹,上杉 薫,長山 和亮
日本機械学会 第33回バイオエンジニアリング講演会, 25 Jun. 2021, 日本機械学会
20210625, 20210626

繰返伸展刺激下での血管平滑筋細胞の内部構造変化の解析　　　　　　　　　　　　　　　
池田圭吾,上杉薫,長山和亮
日本機械学会関東支部 第27期総会・講演会，, 11 Mar. 2021, 日本機械学会
20210310, 20210311

原子間力顕微鏡を用いた骨芽細胞様細胞の骨分化過程における細胞核の力学特性計測　　　　　　　　　　　　　　　
村田博教,長山和亮
日本機械学会関東支部 第27期総会・講演会，, 11 Mar. 2021, 日本機械学会
20210310, 20210311

機械学習を用いた位相差画像からの細胞表面硬さの推定手法の確立　　　　　　　　　　　　　　　
西原賢太,上杉薫,長山和亮,
日本機械学会関東学生会第60回学生員卒業研究発表講演会，, 10 Mar. 2021, 日本機械学会
20210310, 20210310

聴覚を用いた細胞情報評価方法の提案　　　　　　　　　　　　　　　
滝口裕也,長山 和亮,上杉薫
日本機械学会関東学生会第60回学生員卒業研究発表講演会，, 10 Mar. 2021, 日本機械学会
20210310, 20210310

血管力学環境を考慮した生体由来材料による微細溝付細胞培養基質の開発　　　　　　　　　　　　　　　
綿谷直樹,上杉薫,長山和亮
日本機械学会関東学生会第60回学生員卒業研究発表講演会，, 10 Mar. 2021, 日本機械学会
20210310, 20210310

再生皮膚組織の機械的特性評価に適した引張試験システムの開発　　　　　　　　　　　　　　　
喜多則文,武藤潤,長山 和亮,上杉薫
日本機械学会関東学生会第60回学生員卒業研究発表講演会，, 10 Mar. 2021, 日本機械学会
20210310, 20210310

微細溝基板上での血管平滑筋細胞ならびにHeLa細胞の運動解析～細胞種による微細溝環境感知能の違い～（奨励賞論文）　　　　　　　　　　　　　　　
半沢達也,長山和亮
第30回ライフサポート学会フロンティア講演会, 10 Mar. 2021, ライフサポート学会
20210309, 20210310

血管平滑筋細胞の脱分化・老化に伴う張力・運動能力・力学特性の変化,　　　　　　　　　　　　　　　
野上謙三,長山和亮,
日本機械学会 第 31 回バイオフロンティア講演会，, 13 Dec. 2020, 日本機械学会
20201212, 20201213

血管平滑筋細胞の脱分化・老化に伴う 張力・運動能力・力学特性の変化 ,　　　　　　　　　　　　　　　
野上謙三; 長山和亮
日本機械学会 第 31 回バイオフロンティア講演会，, 13 Dec. 2020, 日本機械学会

顕微鏡下マイクロ引張試験機による細胞の力学特性と接着力の実測,~ 細胞種による力学特性・接着特性の違い ~，　　　　　　　　　　　　　　　
小幡祥太,長山和亮
日本機械学会2020年度年次大会,, 15 Sep. 2020, 日本機械学会
20200913, 20200916

微細加工基板による細胞核の局所的な圧縮はDNAの紫外線耐性を向上させる，　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会2020年度年次大会,, 15 Sep. 2020, 日本機械学会

顕微鏡下マイクロ引張試験機の開発と細胞の力学特性と接着力の定量解析～ 細胞種による力学特性・接着特性の違い ～，　　　　　　　　　　　　　　　
小幡祥太; 長山和亮
日本機械学会2020年度年次大会,, 15 Sep. 2020, 日本機械学会

微細溝基板上での細胞運動ならびに内部構造解析に関する研究~細胞種による微細溝感知能の違い~，　　　　　　　　　　　　　　　
半沢達也; 長山和亮
日本機械学会2020年度年次大会,, 15 Sep. 2020, 日本機械学会

顕微鏡下マイクロ引張試験機による細胞の力学特性と接着力の実測 ~ 細胞種による力学特性・接着特性の違い ~，　　　　　　　　　　　　　　　
小幡祥太; 長山和亮
日本機械学会2020年度年次大会,, 15 Sep. 2020, 日本機械学会

顕微鏡下マイクロ引張試験機の開発と細胞の力学特性と接着力の定量解析～ 正常細胞とがん細胞の力学特性・接着特性の違い ～　　　　　　　　　　　　　　　
小幡祥太,長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

原子間力顕微鏡を用いた細胞核の粘弾性計測～ 骨形成細胞の機能変化に対する核の力学構造の関わり ～　　　　　　　　　　　　　　　
村田博教,長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

血管平滑筋細胞の脱分化・老化による細胞内構造の復帰能力の変化，　　　　　　　　　　　　　　　
野上謙三,長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

微細加工基板を用いた細胞核への圧縮負荷による紫外線耐性操作-外力によるDNA凝集操作がUV由来DNA損傷を抑制する-，　　　　　　　　　　　　　　　
三浦光騎,長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

セルソーティング技術への応用を目指した微細溝基板上での細胞運動解析～細胞種ごとの微細溝感知能の違い～　　　　　　　　　　　　　　　
半沢達也,長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

顕微鏡下マイクロ引張試験機の開発と 細胞の力学特性と接着力の定量解析 ～ 正常細胞とがん細胞の力学特性・接着特性の違い ～　　　　　　　　　　　　　　　
小幡祥太; 長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

原子間力顕微鏡を用いた細胞核の粘弾性計測 ～ 骨形成細胞の機能変化に対する 核の力学構造の関わり ～　　　　　　　　　　　　　　　
村田博教; 長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

血管平滑筋細胞の脱分化・老化による 細胞内構造の復帰能力の変化，　　　　　　　　　　　　　　　
野上謙三; 長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

微細加工基板を用いた細胞核への圧縮負荷による 紫外線耐性操作 -外力によるDNA凝集操作がUV由来DNA損傷を抑制する-，　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

セルソーティング技術への応用を目指した 微細溝基板上での細胞運動解析 ～細胞種ごとの微細溝感知能の違い～　　　　　　　　　　　　　　　
半沢達也; 長山和亮
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

組織工学的に構築された皮膚組織の機械的特性評価システムの開発，　　　　　　　　　　　　　　　
喜多則文; 武藤潤; 長山和亮; 上杉薫
日本機械学会2020年度茨城講演会, 21 Aug. 2020, 日本機械学会関東支部

血管平滑筋細胞でのストレスファイバ再構築による形状記憶力解析～細胞の脱分化・老化の影響～　　　　　　　　　　　　　　　
野上謙三; 長山和亮
日本機械学会第33回バイオエンジニアリング講演会，, 14 Jun. 2020, 日本機械学会

細胞の局所的変形が紫外線照射時のDNA損傷に及ぼす影響　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会第33回バイオエンジニアリング講演会，, 14 Jun. 2020, 日本機械学会

骨分化過程における骨芽細胞様細胞の核の力学構造解析　　　　　　　　　　　　　　　
村田博教; 長山和亮
日本機械学会第33回バイオエンジニアリング講演会，, 14 Jun. 2020, 日本機械学会

微細溝基板上での細胞運動解析に関する研究～細胞種による溝感知能の違い～　　　　　　　　　　　　　　　
半沢達也; 長山和亮
日本機械学会第33回バイオエンジニアリング講演会，, 14 Jun. 2020, 日本機械学会

核の変形が細胞の生理機能に与える影響（細胞骨格と核の力学的な繋がり）　　　　　　　　　　　　　　　
長山和亮
日本機械学会第33回バイオエンジニアリング講演会，, 14 Jun. 2020, 日本機械学会

酸性ストレスが細胞周期および細胞運動に与える影響,　　　　　　　　　　　　　　　
佐々木達也; 長山和亮
日本機械学会第32回バイオエンジニアリング講演会，, 20 Dec. 2019, 日本機械学会

Cyclic stretch-induced mechanical stress to the cell nucleus improves the ultraviolet radiation resistance in cells.　　　　　　　　　　　　　　　
Nagayama K; Fukuei T
The 17th International Conference on Biomedical Engineering (ICBME2019), 09 Dec. 2019, BIOMEDICAL ENGINEERING SOCIETY, [Invited]

A novel micro-grooved collagen substrate for inducing vascular smooth muscle cell differentiation through cell tissue arrangement and nucleus remodeling,　　　　　　　　　　　　　　　
Nagayama K
10th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),, 01 Nov. 2019, 10th Asian-Pacific Conference on Biomechanics (AP Biomech 2019),

繰返伸展刺激下での核の力学場の変化が細胞紫外線耐性に与える影響，　　　　　　　　　　　　　　　
長山和亮
日本機械学会2019年度年次大会,, 09 Sep. 2019, 日本機械学会

マイクロピラー基板を用いた核の拘束・変形による細胞の紫外線耐性の変化，　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会2019年度年次大会,, 09 Sep. 2019, 日本機械学会

顕微鏡下マイクロ引張試験機を用いた細胞の力学特性と接着力の実測，　　　　　　　　　　　　　　　
小幡祥太; 長山和亮
日本機械学会2019年度年次大会,, 09 Sep. 2019, 日本機械学会

インプロセス型細胞用力学試験機の開発と細胞の力学特性および接着力の実測，　　　　　　　　　　　　　　　
小幡祥太; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

骨形成遺伝子抑制細胞の核の粘弾性ならびに核内DNAの凝集解析，　　　　　　　　　　　　　　　
村田博教; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

セルソーティング技術への応用を目指した微細溝基板上の細胞運動ならびに内部構造の解析，　　　　　　　　　　　　　　　
半沢達也; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

細胞老化機構の解明を目指した微細加工基板および原子間力顕微鏡による細胞力学解析，　　　　　　　　　　　　　　　
野上謙三; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

病理診断への応用を目指した酸性ストレス下における細胞核の形状解析，　　　　　　　　　　　　　　　
佐々木達也; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

細胞核への力学的負荷が引き起こすDNAの紫外線耐性向上に関する研究，　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会2019年度茨城講演会, 22 Aug. 2019, 日本機械学会関東支部

骨形成遺伝子抑制細胞の核の力学特性ならびに核内DNAの凝集解析　　　　　　　　　　　　　　　
村田博教; 長山和亮
第30回バイオフロンティア講演会, 19 Jul. 2019, 日本機械学会

セルソーティング技術への応用を目指した微細溝基板上での細胞運動解析　　　　　　　　　　　　　　　
半沢達也; 長山和亮
第30回バイオフロンティア講演会, 19 Jul. 2019, 日本機械学会

継代培養での老化に伴う血管平滑筋細胞の張力ならびに力学特性の変化　　　　　　　　　　　　　　　
野上謙三; 長山和亮
第30回バイオフロンティア講演会, 19 Jul. 2019, 日本機械学会

繰返伸展刺激による細胞核の形態変化と細胞紫外線耐性向上の可能性，　　　　　　　　　　　　　　　
長山和亮
第71回日本細胞生物学会大会,, 24 Jun. 2019, 日本生体医工学会大会

繰返伸展刺激による細胞の 紫外線耐性向上に関する研究，　　　　　　　　　　　　　　　
長山和亮
第58回日本生体医工学会大会,, 06 Jun. 2019, 日本生体医工学会大会

繰返伸展刺激による細胞の紫外線耐性向上に関する研究，　　　　　　　　　　　　　　　
長山和亮,
第58回日本生体医工学会大会,, 06 Jun. 2019, 日本生体医工学会大会

疾患発生メカニズム解明のための細胞核の力学特性計測と核内DNAの凝集解析　　　　　　　　　　　　　　　
村田博教; 東 俊文; 長山和亮
日本機械学会関東学生会第58回学生員卒業研究発表講演会，, 18 Mar. 2019, 日本機械学会

細胞の力学特性計測装置の改良と自動化に関する研究　　　　　　　　　　　　　　　
小幡祥太; 大畠成暁; 長山和亮
日本機械学会関東学生会第58回学生員卒業研究発表講演会，, 18 Mar. 2019, 日本機械学会

微細加工基板を用いた細胞核への圧縮負荷による細胞の紫外線耐性向上に関する研究　　　　　　　　　　　　　　　
三浦光騎; 長山和亮
日本機械学会関東学生会第58回学生員卒業研究発表講演会，, 18 Mar. 2019, 日本機械学会

微細溝基質の機械特性を利用した細胞運動制御の研究　　　　　　　　　　　　　　　
半沢達也; 長山和亮
日本機械学会関東学生会第58回学生員卒業研究発表講演会，, 18 Mar. 2019, 日本機械学会

細胞の老化に注目した細胞の形態・張力・運動能力の解析　　　　　　　　　　　　　　　
野上謙三; 長山和亮
日本機械学会関東学生会第58回学生員卒業研究発表講演会，, 18 Mar. 2019, 日本機械学会

微細溝基板上での正常血管細胞およびがん細胞の運動解析　　　　　　　　　　　　　　　
半沢達也; 長山和亮
第28回ライフサポート学会フロンティア講演会, 15 Mar. 2019, ライフサポート学会

継代培養による細胞老化に伴う血管細胞の形態・張力・運動能力の変化　　　　　　　　　　　　　　　
野上謙三; 長山和亮
第28回ライフサポート学会フロンティア講演会, 15 Mar. 2019, ライフサポート学会

細胞用引張試験機の開発とこれを用いた血管平滑筋細胞の硬さと接着力の実測（奨励賞論文）　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
第28回ライフサポート学会フロンティア講演会, 15 Mar. 2019, ライフサポート学会

力学的側面からの細胞放射線耐性制御技術の開発を目指して　　　　　　　　　　　　　　　
長山和亮
第12 回Quantum Medicine 研究会「細胞の放射線感受性に対する影響要因」，, 17 Feb. 2019, 茨城大学理学部公開シンポジウム

巨視的引張環境下における配列化培養血管平滑筋細胞内の核の変形解析　　　　　　　　　　　　　　　
尾崎康史; 長山和亮
日本機械学会第31回バイオエンジニアリング講演会，, 14 Dec. 2018, 日本機械学会

原子間力顕微鏡を用いた細胞内のｱｸﾁﾝｽﾄﾚｽﾌｧｲﾊﾞと核の結合状態の推察　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
日本機械学会第31回バイオエンジニアリング講演会，, 14 Dec. 2018, 日本機械学会

血管平滑筋分化における核内外の力学環境の変化　　　　　　　　　　　　　　　
長山和亮; 佐藤亜希子
日本機械学会第31回バイオエンジニアリング講演会，, 14 Dec. 2018, 日本機械学会

細胞周期における細胞核の形態変化把握による細胞状態の識別　　　　　　　　　　　　　　　
佐々木達也; 長山和亮
第29回バイオフロンティア講演会, 24 Oct. 2018, 日本機械学会

血管平滑筋細胞の分化に伴う細胞の形状および収縮能変化の解析　　　　　　　　　　　　　　　
辰野晴信; 長山和亮
第29回バイオフロンティア講演会, 24 Oct. 2018, 日本機械学会

細胞用引張試験機および原子間力顕微鏡を用いた血管平滑筋細胞の巨視的・微視的力学解析　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
第29回バイオフロンティア講演会, 24 Oct. 2018, 日本機械学会

細胞核の力学的拘束による紫外線由来DNA切断損傷の抑制　　　　　　　　　　　　　　　
長山和亮; 佐川千秋
日本機械学会2018年度年次大会,, 09 Sep. 2018, 日本機械学会

細胞への繰返伸展刺激が紫外線由来DNA損傷を抑制するメカニズム　　　　　　　　　　　　　　　
長山和亮; 福栄智大
日本機械学会2018年度年次大会,, 09 Sep. 2018, 日本機械学会

細胞運命予測を目指した細胞核の形態ﾃﾞｰﾀﾍﾞｰｽ構築に関する基礎研究　　　　　　　　　　　　　　　
佐々木達也; 長山和亮
日本機械学会第26回茨城講演会, 22 Aug. 2018, 日本機械学会関東支部

細胞の形状に着目した細胞張力顕微鏡観察法による張力解析　　　　　　　　　　　　　　　
辰野晴信; 長山和亮
日本機械学会第26回茨城講演会, 22 Aug. 2018, 日本機械学会関東支部

血管平滑筋細胞の配列・組織化培養技術の開発および力学解析　　　　　　　　　　　　　　　
尾崎康史; 長山和亮
日本機械学会第26回茨城講演会, 22 Aug. 2018, 日本機械学会関東支部

ﾒｶﾉﾄﾗﾝｽﾀﾞｸｼｮﾝの解明に向けた細胞の巨視的・微視的力学解析　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
日本機械学会第26回茨城講演会, 22 Aug. 2018, 日本機械学会関東支部

Nuclear-cytoskeletal Interactions in Vascular Smooth Muscle Cells:Possible Roles in the Regulation of Cell Differentiation　　　　　　　　　　　　　　　
Nagayama K
8th World Congress of Biomechanics (WCB2018),, 08 Jul. 2018, 8th World Congress of Biomechanics (WCB2018)，

Investigation of the nuclear-cytoskeletal interactions in vascular smooth muscle cell differentiationusing a novel micro-grooved collagen substrate,　　　　　　　　　　　　　　　
Nagayama K
8th World Congress of Biomechanics (WCB2018),, 08 Jul. 2018, 8th World Congress of Biomechanics (WCB2018)，

微細溝コラーゲン基質を用いた血管平滑筋細胞の配列培養組織形成と核のﾒｶﾉﾄﾗﾝｽﾀﾞｸｼｮﾝ解析　　　　　　　　　　　　　　　
長山和亮
第57回日本生体医工学会大会,, 19 Jun. 2018, 日本生体医工学会大会

細胞への力学刺激が紫外線由来DNA損傷を抑制するメカニズムの実験的考察　　　　　　　　　　　　　　　
長山和亮; 福栄智大
日本機械学会関東支部 第24期総会・講演会,, 17 Mar. 2018, 日本機械学会

細胞用マイクロ引張試験機を用いた細胞のスティフネスと接着力の定量解析　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
日本機械学会関東支部 第24期総会・講演会,, 17 Mar. 2018, 日本機械学会

コラーゲン微細溝基質を用いた配列化培養が血管平滑筋細胞の分化ならびに力学特性に与える影響　　　　　　　　　　　　　　　
尾崎康史; 内田敬一; 長山和亮
日本機械学会関東支部 第24期総会・講演会,, 17 Mar. 2018, 日本機械学会

マイクロピラー基板を用いた核の変形・拘束による核内DNA凝集操作に関する研究～細胞周期・紫外線耐性に与える影響～　　　　　　　　　　　　　　　
佐川千秋; 長山和亮
日本機械学会第30回バイオエンジニアリング講演会，, 14 Dec. 2017, 日本機械学会

繰返引張刺激による細胞の紫外線耐性向上の可能性　　　　　　　　　　　　　　　
福栄智大; 長山和亮
日本機械学会第30回バイオエンジニアリング講演会，, 14 Dec. 2017, 日本機械学会

細胞配列・運動におけるアクチン細胞骨格と核の機械的結合の重要性　　　　　　　　　　　　　　　
長山和亮
日本機械学会第30回バイオエンジニアリング講演会，, 14 Dec. 2017, 日本機械学会

Investigation of the nuclear-cytoskeletal interactions in vascular smooth muscle cells cultured on a micro-grooved collagen substrate　　　　　　　　　　　　　　　
Kazuaki Nagayama; Keiichi Uchida; Saki Inaba Takeuchi
5th Switzerland-Japan Workshop on Biomechanics 2017 (SJB2017), 14 Sep. 2017, Switzerland-Japan Society on Biomechanics, [Invited]

Estimation of flow- induced deformation of glycocalyx layer on vascular endothelial cells: comparison of three methods　　　　　　　　　　　　　　　
Takeo Matsumoto; Yutaka Takahashi; Yasushi Owaki; Kazuaki Nagayama
5th Switzerland-Japan Workshop on Biomechanics 2017 (SJB2017), 14 Sep. 2017, Switzerland-Japan Society on Biomechanics, [Invited]

コラーゲン微細溝基質を用いた血管平滑筋細胞の配列化培養と核に加わる力の実験的考察　　　　　　　　　　　　　　　
長山和亮; 内田 敬一; 竹内 早希
日本機械学会2017年度年次大会, 04 Sep. 2017, 日本機械学会

微細加工基板を用いた核への直接的変形・拘束による細胞紫外線耐性制御の試み　　　　　　　　　　　　　　　
佐川千秋; 長山和亮
日本機械学会第25回茨城講演会, 29 Aug. 2017, 日本機械学会関東支部

繰返引張刺激による細胞の構造変化と細胞紫外線耐性への影響　　　　　　　　　　　　　　　
福栄智大; 長山和亮
日本機械学会第25回茨城講演会, 29 Aug. 2017, 日本機械学会関東支部

コラーゲン微細溝基質を用いた血管平滑筋細胞の配列化培養と力学特性解析　　　　　　　　　　　　　　　
尾崎康史; 内田敬一; 長山和亮
日本機械学会第25回茨城講演会, 29 Aug. 2017, 日本機械学会関東支部

細胞用マイクロ引張試験機と原子間力顕微鏡を用いた細胞力学特性の統合解析　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
日本機械学会第25回茨城講演会, 29 Aug. 2017, 日本機械学会関東支部

The biomechanical effects of the deformation and trapping of the nucleus on cellular UV resistance　　　　　　　　　　　　　　　
Nagayama K; Sagawa C
26th Congress of the International Society of Biomechanics, 24 Jul. 2017, the International Society of Biomechanics, [Invited]

細胞核の力学場が細胞紫外線耐性に与える影響　　　　　　　　　　　　　　　
長山和亮; 佐川千秋
第56回日本生体医工学会大会, 03 May 2017, 日本生体医工学会大会

細胞内微細構造の力学特性計測を目指したマイクロ力学試験機の開発　　　　　　　　　　　　　　　
大畠成暁; 長山和亮
第26回ライフサポート学会フロンティア講演会, 10 Mar. 2017, ライフサポート学会

血管壁内細胞配列を考慮したコラーゲン微細溝基質の開発とこれを用いた血管平滑筋細胞の分化制御の試み　　　　　　　　　　　　　　　
内田敬一; 長山和亮
第26回ライフサポート学会フロンティア講演会, 10 Mar. 2017, ライフサポート学会

核の変形が細胞の生理機能に及ぼす影響　　　　　　　　　　　　　　　
長山和亮
日本機械学会第29回バイオエンジニアリング講演会, 20 Jan. 2017, 日本機械学会

The biomechanical effects of the deformation and trapping of the nucleus on cellular functions.　　　　　　　　　　　　　　　
Nagayama K; Sagawa C
The 16th International Conference on Biomedical Engineering (ICBME2016), 07 Dec. 2016, BIOMEDICAL ENGINEERING SOCIETY, [Invited]

Control of vascular smooth muscle cell differentiation using a novel micro-grooved collagen substrate　　　　　　　　　　　　　　　
Nagayama K
第54回日本生物物理学会大会, 25 Nov. 2016, 日本生物物理学会

血管壁内細胞配列を考慮したコラーゲン微細溝基質による平滑筋細胞培養系の確立　　　　　　　　　　　　　　　
内田敬一; 長山和亮
第27回バイオフロンティア講演会, 22 Oct. 2016, 日本機械学会

核の力学的拘束・変形による核内DNA の分布・凝集の変化が細胞紫外線耐性に与える影響　　　　　　　　　　　　　　　
佐川千秋; 長山和亮
第27回バイオフロンティア講演会, 22 Oct. 2016, 日本機械学会

繰返引張ひずみによる細胞内の構造変化と細胞紫外線耐性向上の可能性　　　　　　　　　　　　　　　
福栄智大; 長山和亮
第27回バイオフロンティア講演会, 22 Oct. 2016, 日本機械学会

繰返ひずみ場における細胞組織の創傷治癒運動の解析　　　　　　　　　　　　　　　
長山和亮; 鈴木悠也
日本機械学会2016年度年次大会, 11 Sep. 2016, 日本機械学会

微細加工基質を利用した力学的側面からの細胞機能計測・制御技術の開発　　　　　　　　　　　　　　　
長山和亮
2016年度精密工学会秋季大会, 07 Sep. 2016, 精密工学会

血管力学環境を考慮した細胞培養系の確立と細胞内での力学刺激伝達メカニズムの考察　　　　　　　　　　　　　　　
内田敬一; 長山和亮
日本機械学会第24回茨城講演会, 26 Aug. 2016, 日本機械学会関東支部

力学刺激が細胞組織の紫外線耐性に与える影響に関する研究　　　　　　　　　　　　　　　
福栄智大; 長山和亮
日本機械学会第24回茨城講演会, 26 Aug. 2016, 日本機械学会関東支部

微細加工基板を用いた細胞核内のDNA分布・凝集操作に関する研究(細胞の紫外線耐性向上の可能性)　　　　　　　　　　　　　　　
佐川千秋; 長山和亮
日本機械学会第24回茨城講演会, 26 Aug. 2016, 日本機械学会関東支部

A Study For The Effects Of The Mechanical Trapping Of The Nucleus On Cellular Events Using A Micropillar Substrate　　　　　　　　　　　　　　　
Nagayama K
The 2016 Summer Biomechanics, Bioengineering and Biotransport Conference (SB3C2016), 29 Jun. 2016, ASME

微細加工基板を用いた細胞核の機械的変形・拘束が細胞機能に与える影響の検討　　　　　　　　　　　　　　　
長山和亮; 佐川千秋
第55回日本生体医工学会大会, 26 Apr. 2016, 日本生体医工学会大会

微細な力学環境が 細胞の機能に与える影響　　　　　　　　　　　　　　　
長山和亮
第29回テクニスト研究会, 22 Apr. 2016, テクニスト研究会, [Invited]

微細な力学環境が細胞の機能に与える影響　　　　　　　　　　　　　　　
長山和亮
第29回テクニスト研究会, 22 Apr. 2016, テクニスト研究会, [Invited]

微細加工基板を用いた細胞核の変形・拘束が細胞紫外線耐性に与える影響　　　　　　　　　　　　　　　
佐川千秋; 長山和亮
第25 回ライフサポート学会フロンティア講演会, 08 Mar. 2016, 日本生物物理学会

細胞組織の創傷治癒運動に対する繰返引張ひずみ刺激の影響　　　　　　　　　　　　　　　
鈴木悠也; 長山和亮
第25 回ライフサポート学会フロンティア講演会, 08 Mar. 2016, 日本生物物理学会

細胞組織の運動・配列制御を目指したコラーゲン微細溝基質の開発　　　　　　　　　　　　　　　
島田快; 長山和亮
第25 回ライフサポート学会フロンティア講演会, 08 Mar. 2016, 日本生物物理学会

繰返引張刺激が細胞の紫外線耐性に与える影響　　　　　　　　　　　　　　　
福栄智大; 長山和亮
第25 回ライフサポート学会フロンティア講演会, 08 Mar. 2016, 日本生物物理学会

細胞核の変形の生理学的意義に関する実験的考察　　　　　　　　　　　　　　　
長山和亮
日本機械学会第28回バイオエンジニアリング講演会, 09 Jan. 2016, 日本機械学会

繰返引張ひずみ場での細胞組織の再配列原理の理解　　　　　　　　　　　　　　　
長山和亮
日本機械学会 M&M2015材料力学ｶﾝﾌｧﾚﾝｽ, 21 Nov. 2015, 日本機械学会関東支部

Nuclear-cytoskeletal Interactions in Vascular Smooth MuscleCells: Possible Roles in the Regulation of Cell Differentiation　　　　　　　　　　　　　　　
Nagayama K
The International Conference on Advanced Technology in Experimental Mechanics 2015 (ATEM’15), 04 Nov. 2015, 日本機械学会, [Invited]

Spatiotemporal Dynamics of Actin during Adhesion Process ofMC3T3-E1 Cells to Substrate　　　　　　　　　　　　　　　
Wang J; Nagayama K; Matsumoto T
The International Conference on Advanced Technology in Experimental Mechanics 2015 (ATEM’15), 04 Nov. 2015, 日本機械学会

Nuclear mechanics and mechanotransduction- the role of the nuclear deformability in cell proliferation　　　　　　　　　　　　　　　
NagayamaK; Murakami Y; Hamaji Y; Sato Y; Matsumoto T
8th Asian-Pacific Conference on Biomechanics, 16 Sep. 2015, Asian-Pacific Conference on Biomechanics Society, [Invited]

Dynamics of actin filaments during adhesion process of MC3T3E-1 cells to substrate　　　　　　　　　　　　　　　
Wang J; Sugita S; Nagayama K; Matsumoto T
8th Asian-Pacific Conference on Biomechanics, 16 Sep. 2015, Asian-Pacific Conference on Biomechanics Society, [Invited]

マイクロピラーによる細胞核の力学的拘束は正常細胞の増殖を抑制するが腫瘍細胞には影響しない　　　　　　　　　　　　　　　
長山和亮; 濱路祐未; 佐藤祐次; 松本健郎
第53回日本生物物理学会年会, 13 Sep. 2015, 日本生物物理学会

3次元環境下で培養した血管平滑筋細胞の力学情報伝達機構の解析　　　　　　　　　　　　　　　
内田敬一; 長山和亮
日本機械学会第23回茨城講演会, 28 Aug. 2015, 日本機械学会関東支部

微細加工基板を用いた細胞核の機械的拘束と細胞増殖性への影響　　　　　　　　　　　　　　　
長山和亮
日本機械学会第23回茨城講演会, 28 Aug. 2015, 日本機械学会関東支部

細胞機能操作・診断ツールとしての磁気駆動MEMSデバイス開発　　　　　　　　　　　　　　　
長山和亮
日本機械学会第23回茨城講演会, 28 Aug. 2015, 日本機械学会関東支部

マイクロピラー基板を用いた細胞核の機械的拘束と細胞増殖性への影響　　　　　　　　　　　　　　　
長山和亮
第54回日本生体医工学会大会, 07 May 2015, 日本生体医工学会大会

細胞の基板付着・伸展過程における焦点接着斑の形態変化の観察　　　　　　　　　　　　　　　
王軍鋒; 杉田修啓; 長山和亮; 松本健郎
第54回日本生体医工学会大会, 07 May 2015, 日本生体医工学会大会

家兎総頸動脈におけるin situ FMD再現系の構築　　　　　　　　　　　　　　　
矢口俊之; 河口磨紀; 杉田修啓; 長山和亮; 松本健郎
第54回日本生体医工学会大会, 07 May 2015, 日本生体医工学会大会

２種のラット腹部大動脈瘤モデル間の弾性線維量と力学特性の差異　　　　　　　　　　　　　　　
杉田修啓; 松川瞬; 長山和亮; 松本健郎
第54回日本生体医工学会大会, 07 May 2015, 日本生体医工学会大会

３次元培養細胞を用いた細胞内の力学情報伝達機構の解析　　　　　　　　　　　　　　　
内田敬一; 長山和亮
日本機械学会 関東学生会第54回学生員卒業研究発表講演会, 20 Mar. 2015, 日本機械学会

ひずみ場操作による細胞分裂制御に関する基礎研究　　　　　　　　　　　　　　　
髙良亮太; 長山和亮
日本機械学会 関東学生会第54回学生員卒業研究発表講演会, 20 Mar. 2015, 日本機械学会

力学刺激による骨芽細胞の組織構造制御に関する基礎研究　　　　　　　　　　　　　　　
市塚博季; 長山和亮
日本機械学会 関東学生会第54回学生員卒業研究発表講演会, 20 Mar. 2015, 日本機械学会

磁性体を用いた細胞核への力学刺激負荷に関する研究　　　　　　　　　　　　　　　
伊藤奎昌; 長山和亮
日本機械学会 関東学生会第54回学生員卒業研究発表講演会, 20 Mar. 2015, 日本機械学会

微細加工基板を用いた細胞核の力学環境制御と細胞機能への影響の調査　　　　　　　　　　　　　　　
村上裕貴; 長山和亮
日本機械学会 関東学生会第54回学生員卒業研究発表講演会, 20 Mar. 2015, 日本機械学会

細胞の機能調整に関わる核と細胞骨格の相互作用　　　　　　　　　　　　　　　
長山和亮
日本機械学会第27回バイオエンジニアリング講演会, 09 Jan. 2015, 日本機械学会

アクチン細胞骨格と核との力学的結合が血管平滑筋細胞の分化に与える影響　　　　　　　　　　　　　　　
長山和亮; 岩田 誠; 松本健郎
日本生物物理学会第52回年会, 25 Sep. 2014, 日本生物物理学会

基板接着に伴う細胞内焦点接着斑の形態変化の観察　　　　　　　　　　　　　　　
王 軍鋒; 長山和亮; 松本健郎
日本機械学会2014年度年次大会, 07 Sep. 2014, 日本機械学会

細胞の力学応答解析ツールとしての磁気駆動式マイクロピラー基板の開発　　　　　　　　　　　　　　　
長山和亮; 井上卓也; 松本健郎
日本機械学会第22回茨城講演会, 05 Sep. 2014, 日本機械学会関東支部

Analysis of the Cytoskeleton-Nucleus Mechanotransduction Pathway: Direct Force Transmission from the Actin Stress Fibers to the Nucleus　　　　　　　　　　　　　　　
Nagayama K; Yamasaki S; Yahiro Y; Matsumoto T
The 4th Japan-Switzerland Workshop on Biomechanics, 01 Sep. 2014, Society of the Japan-Switzerland Workshop on Biomechanics, [Invited]

Mechanical interaction between actin stress fibers and the nucleus: Direct force transmission from the whole-cell level to the nucleus　　　　　　　　　　　　　　　
Nagayama K; Yahiro Y; Yamasaki S; Matsumoto T
The 7th World Congress of Biomechanics (WBC2014), 06 Jul. 2014, Society of the World Congress of Biomechanics, [Invited]

Changes in the mechanical environment of nucleus during the phenotypic changes of vascular smooth muscle cells　　　　　　　　　　　　　　　
Nagayama K; Iwata M; Hamaji Y; Matsumoto T
International Symposium on Mechanobiology 2014 (ISMB2014), 20 May 2014, Society of the International Symposium on Mechanobiology, [Invited]

Apr. 2017 - Present, 日本細胞生物学会

Apr. 2016 - Present, 精密工学会

2011 - Present, Biophysical Society

2011 - Present, Biomedical Engineering Society

2009 - Present, 日本生物物理学会

2008 - Present, American Physiological Society

2005 - Present, 日本再生医療学会

2003 - Present, 日本生体医工学会

2002 - Present, 日本機械学会

細胞骨格と核の「繋がり」に基づく生体恒常性維持・破綻メカニズムの解明
基盤研究(B)
茨城大学
Apr. 2024 - Mar. 2027

力学的・幾何学的側面からの細胞機能情報高精度診断プラットフォームの創成　　　　　　　　　　　　　　　
Apr. 2025 - Mar. 2026

Understanding the failure process of soft biological materials - Why does a minor injury lead to fatal tissue damage?
Grant-in-Aid for Scientific Research (B)
Tottori University
Apr. 2023 - Mar. 2026

生物表面に存在する微細構造の変形と接着/摩擦機能を同時に評価できるシステムの開発
基盤研究(C)
茨城大学
Apr. 2022 - Mar. 2025

〔Major achievements〕Study on the switching mechanism of structural and tensional memory of cells
Grant-in-Aid for Challenging Research (Exploratory)
Ibaraki University
Jun. 2022 - Mar. 2024

〔Major achievements〕機能ゲノミクス解析とハイスループット解析を用いた線維性異形成症新規治療法開発
基盤研究(B)
東京歯科大学
Apr. 2021 - Mar. 2024

〔Major achievements〕血管壁の恒常性維持と病態形成におけるメカノトランスダクション機序の解明　　　　　　　　　　　　　　　
基盤研究(B)
Apr. 2021 - Mar. 2024

〔Major achievements〕細胞骨格と核の「繋がり」に基づく細胞の恒常性維持機構の解明　　　　　　　　　　　　　　　
基盤研究(B)
Apr. 2021 - Mar. 2024

〔Major achievements〕茨城大学特色研究加速イニシアティブ「生体組織に備わるとされる力学的適応能力に関する研究」　　　　　　　　　　　　　　　
特色研究加速イニシアティブ
Apr. 2021 - Mar. 2022

〔Major achievements〕細胞の”構造と力の記憶”メカニズムの探求　　　　　　　　　　　　　　　
挑戦的研究（萌芽）
Jun. 2019 - Mar. 2021

血管疾患発生機構の解明に向けた組織・細胞・核のメカノトランスダクションの統合解析技術の開発　　　　　　　　　　　　　　　
Dec. 2015 - Mar. 2021

〔Major achievements〕核の力学場に立脚した細胞の放射線耐性調整機構の解明　　　　　　　　　　　　　　　
基盤研究(B)
Apr. 2017 - Mar. 2020

〔Major achievements〕細胞の”構造と力の記憶”メカニズムを探る　　　　　　　　　　　　　　　
挑戦的萌芽研究
Apr. 2016 - Mar. 2018

〔Major achievements〕茨城大学イノベーション研究推進プログラム・異分野融合研究・「生体組織の力学的な秩序形成に基づいた 疾患進行・創傷治癒メカニズムの解明」　　　　　　　　　　　　　　　
Dec. 2014 - Mar. 2016

茨城大学イノベーション研究推進プログラム・萌芽的研究・「細胞機能操作・診断ツールとしての MEMS アクチュエータデバイスの技術展開」　　　　　　　　　　　　　　　
Dec. 2014 - Mar. 2016

〔Major achievements〕細胞核内外の力学環境操作による細胞機能制御の試み　　　　　　　　　　　　　　　
Grant-in-Aid for Exploratory Research
Apr. 2014 - Mar. 2016

〔Major achievements〕細胞の力学応答機構解明のための細胞骨格～核膜～ＤＮＡの力学的相互作用の解析　　　　　　　　　　　　　　　
Grant-in-Aid for Young Scientists(A)
Apr. 2012 - Mar. 2016

〔Major achievements〕生体組織の力学的な秩序形成に基づいた疾患進行・創傷治癒メカニズムの解明　　　　　　　　　　　　　　　
茨城大学イノベーション研究推進プログラム異分野連携・融合研究
Dec. 2014 - Mar. 2015

細胞機能操作・診断ツールとしてのMEMS アクチュエータデバイスの技術展開　　　　　　　　　　　　　　　
茨城大学イノベーション研究推進プログラム萌芽的研究
Dec. 2014 - Mar. 2015

細胞機能操作・診断ツールとしての磁気駆動式MEMSデバイスの開発　　　　　　　　　　　　　　　
ライフサポート科学重点研究 サブプロジェクト研究奨励
Apr. 2014 - Mar. 2015

細胞運動の秩序を担う細胞接着斑・細胞骨格・核の力学的協調作用の解析　　　　　　　　　　　　　　　
Grant-in-Aid for Scientific Research on Priority Areas
Apr. 2013 - Mar. 2015

〔Major achievements〕細胞内張力分布の直接的操作による細胞分裂制御の試み　　　　　　　　　　　　　　　
Grant-in-Aid for Exploratory Research
Apr. 2012 - Mar. 2014

〔Major achievements〕細胞核の形態操作と核への力学刺激負荷による細胞機能制御の試み　　　　　　　　　　　　　　　
Grant-in-Aid for Exploratory Research
Apr. 2010 - Mar. 2012

〔Major achievements〕細胞の力学応答機構解明を目指した細胞内残留応力場のその場計測手法の確立　　　　　　　　　　　　　　　
Grant-in-Aid for Young Scientists(A)
Apr. 2008 - Mar. 2012

〔Major achievements〕核内外の力学要素の探索と核の応力場解析　　　　　　　　　　　　　　　
Grant-in-Aid for Scientific Research on Priority Areas
Apr. 2009 - Mar. 2011

〔Major achievements〕細胞分裂機構の解明を目指した細胞焦点接着斑力学刺激負荷デバイスの開発　　　　　　　　　　　　　　　
Grant-in-Aid for Exploratory Research
Apr. 2007 - Mar. 2009

〔Major achievements〕マイクロパターニングと力学刺激負荷による血管平滑筋細胞の形質転換メカニズムの解明　　　　　　　　　　　　　　　
Grant-in-Aid for Young Scientists(B)
Apr. 2005 - Mar. 2007