Biomechanical analysis of the nuclear-cytoskeletal interactions to elucidate the cellular mechanotransduction mechanism

• Project/Area Number: 24680051
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Ibaraki University (2014-2015); Nagoya Institute of Technology (2012-2013)
• Principal Investigator: NAGAYAMA KAZUAKI 茨城大学, 工学部, 教授 (10359763)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥26,520,000 (Direct Cost: ¥20,400,000、Indirect Cost: ¥6,120,000); Fiscal Year 2015: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2012: ¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
• Keywords: 細胞バイオメカニクス / メカノバイオロジー / 細胞骨格 / 細胞核 / DNA / メカノトランスダクション / 生体計測 / バイオメカニクス / 生体・情報計測

Outline of Final Research Achievements

The purpose of this study is to investigate the roles of the nuclear-cytoskeletal interactions in vascular smooth muscle differentiation. We found that mechanical interaction between actin cytoskeleton and the nucleus significantly increased and chromatin condensation could be observed clearly during smooth muscle differentiation. The cell tissue orientation and cyclic stretch mechanical stimulation also induced the nuclear-cytoskeletal interactions and induced the smooth muscle differentiation. The results of this study will provide new prospects of cellular mechanotransduction mechanism.

Research Products

• [Journal Article] Dynamics of actin filaments of MC3T3-E1 cells during adhesion process to substrate (2016)
  • Author(s): J Wang, S Sugita, K Nagayama, T Matsumoto
  • Journal Title: Journal of Biomechanical Science and Engineering Volume: 11 Issue: 2 Pages: 15-00637-15-00637
  • DOI: 10.1299/jbse.15-00637
  • NAID: 130005158997
  • ISSN: 1880-9863
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Mechanical trapping of the nucleus on micropillared surfaces inhibits the proliferation of vascular smooth muscle cells but not cervical cancer HeLa cells (2015)
  • Author(s): Nagayama K, Hamaji Y, Sato Y, Matsumoto T
  • Journal Title: J Biomechanics Volume: 48 Issue: 10 Pages: 1796-1803
  • DOI: 10.1016/j.jbiomech.2015.05.004
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Multiphasic Stress Relaxation Response of Freshly Isolated and Cultured Vascular Smooth Muscle Cells Measured by Quasi-In Situ Tensile Test (2015)
  • Author(s): Nagayama K, Saito S, Matsumoto T
  • Journal Title: Bio-Medical Materials and Engineering Volume: 25 Issue: 3 Pages: 299-312
  • DOI: 10.3233/bme-151276
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Quantitative analysis of cellular traction forces using a micropillar substrate and estimation of the intracellular force applied to the nucleus (2015)
  • Author(s): 長山和亮
  • Journal Title: Transactions of the JSME (in Japanese) Volume: 81 Issue: 824 Pages: 14-00692-14-00692
  • DOI: 10.1299/transjsme.14-00692
  • NAID: 130005066603
  • ISSN: 2187-9761
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 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 (2015)
  • Author(s): 王軍鋒, 杉田修啓, 長山和亮, 松本健郎
  • Journal Title: 生体医工学 Volume: 53-6 Pages: 311-318
  • NAID: 130005155604
  • Peer Reviewed
• [Journal Article] 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 (2015)
  • Author(s): 長山和亮，松本健郎
  • Journal Title: ファルマシア Volume: 51-11 Pages: 1066-1068
  • NAID: 130007447965
  • Peer Reviewed
• [Journal Article] Estimation of the mechanical connection between apical stress fibers and the nucleus in vascular smooth muscle cells cultured on a substrate (2014)
  • Author(s): K Nagayama, S Yamazaki, Y Yahiro, T Matsumoto
  • Journal Title: Journal of Biomechanics Volume: Vol.47 Pages: 1422-1429
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Estimation of the mechanical connection between apical stress fibers and the nucleus in vascular smooth muscle cells cultured on a substrate (2014)
  • Author(s): Nagayama K, Yamazaki S, Yahiro Y, Matsumoto T.
  • Journal Title: J Biomechanics Volume: 47 Issue: 6 Pages: 1422-29
  • DOI: 10.1016/j.jbiomech.2014.01.042
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Left-right asymmetry is formed in individual cells by intrinsic cell chirality (2014)
  • Author(s): Hatori, R., Ando, T., Sasamura, T., Nakazawa, N., Nakamura, M., Taniguchi, K., Hozumi, S., Kikuta, J., Ishii, M., *Matsuno, K.
  • Journal Title: Mech Dev Volume: 133 Issue: 2 Pages: 482-95
  • DOI: 10.1016/j.ydbio.2013.07.023
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 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 (2013)
  • Author(s): 長山和亮
  • Journal Title: 人工臓器 Volume: 42-3号 Pages: 205-208
  • NAID: 130003395322
• [Journal Article] Apical and basal stress fibers have different roles on mechanical regulation of the nucleus in vascular smooth muscle cells (2013)
  • Author(s): Nagayama K, Yahiro Y, Matsumoto T
  • Journal Title: Cellular and Molecular Bioengineering Volume: 6 Issue: 4 Pages: 463-481
  • DOI: 10.1007/s12195-013-0294-7
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Haemodynamically dependent valvulogenesis of zebrafish heart is mediated by flow-dependent expression of miR-21 (2013)
  • Author(s): Banjo T, Grajcarek J, Yoshino D, Osada H, Miyasaka KY, Kida YS, Ueki Y, Nagayama K Kawakami K, Matsumoto T, Sato M, Ogura T
  • Journal Title: Nature Communications Volume: 4,1978 Issue: 1 Pages: 1978-1978
  • DOI: 10.1038/ncomms2978
  • Peer Reviewed / Open Access
• [Journal Article] ヒト橈骨動脈の力学特性の非侵襲計測法の確立と力学特性に対する平滑筋収縮状態の影響評価 (2013)
  • Author(s): 矢口俊之
  • Journal Title: ライフサポート Volume: 25-4 Pages: 143-150
  • Peer Reviewed
• [Journal Article] Low-flow-resistance Methacrylate-based Polymer Monolithic Column Prepared by Low-conversion Ultraviolet Photopolymerization at Low Temperature (2013)
  • Author(s): Tomohiko HIRANO
  • Journal Title: Analytical Sciences Volume: 29 Issue: 2 Pages: 205-211
  • DOI: 10.2116/analsci.29.205
  • NAID: 10031156857
  • ISSN: 0910-6340, 1348-2246
  • Peer Reviewed
• [Journal Article] Strain waveform dependence of stress fiber reorientation in cyclically stretched osteoblastic cells : Effects of viscoelastic compression of stress fibers (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Journal Title: American Journal of Physiology, Cell Physiology Volume: 302 Pages: 1469-1478
  • Peer Reviewed
• [Journal Article] Dynamic Changes of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate: Tensional Homeostasis of Aortic Smooth Muscle Cells (2012)
  • Author(s): Nagayama, K., Adachi, A., Matsumoto, T.
  • Journal Title: Journal of Biomechanical Science and Engineering Volume: 7 Issue: 2 Pages: 130-140
  • DOI: 10.1299/jbse.7.130
  • NAID: 130002066897
  • ISSN: 1880-9863
  • Peer Reviewed
• [Journal Article] Development of a Novel Magnetic-Driven Micropillar Substrate for Mechanical Stimulation at Individual Focal Adhesions of Cells (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Journal Title: Proceedings of the 2012 Summer Bioengineering Conference
  • Peer Reviewed
• [Presentation] 細胞核の変形の生理学的意義に関する実験的考察 (2016)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会 第28回バイオエンジニアリング講演会
  • Place of Presentation: 東京
  • Year and Date: 2016-01-09
• [Presentation] 繰返引張ひずみ場での細胞組織の再配列原理の理解 (2015)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会 M&M2015材料力学カンファレンス
  • Place of Presentation: 東京
  • Year and Date: 2015-11-21
• [Presentation] Nuclear-cytoskeletal Interactions in Vascular Smooth MuscleCells: Possible Roles in the Regulation of Cell Differentiation (2015)
  • Author(s): K Nagayama
  • Organizer: The International Conference on Advanced Technology in Experimental Mechanics 2015 (ATEM’15)
  • Place of Presentation: Toyohashi
  • Year and Date: 2015-11-04
  • Int'l Joint Research / Invited
• [Presentation] Dynamics of Actin during Adhesion Process ofMC3T3-E1 Cells to Substrate (2015)
  • Author(s): J Wang, Nagayama, T Matsumoto
  • Organizer: The International Conference on Advanced Technology in Experimental Mechanics 2015 (ATEM’15)
  • Place of Presentation: Toyohashi
  • Year and Date: 2015-11-04
  • Int'l Joint Research
• [Presentation] Nuclear mechanics and mechanotransduction- the role of the nuclear deformability in cell proliferation - (2015)
  • Author(s): K Nagayama, Y Murakami, Y Hamaji, Y Sato, T Matsumoto
  • Organizer: 8th Asian-Pacific Conference on Biomechanics
  • Place of Presentation: Sapporo
  • Year and Date: 2015-09-16
  • Int'l Joint Research / Invited
• [Presentation] Dynamics of actin filaments during adhesion process of MC3T3E-1 cells to substrate (2015)
  • Author(s): J Wang, S Sugita, K Nagayama, T Matsumoto
  • Organizer: 8th Asian-Pacific Conference on Biomechanics
  • Place of Presentation: Sapporo
  • Year and Date: 2015-09-16
  • Int'l Joint Research
• [Presentation] 細胞の機能調整に関わる核と細胞骨格の相互作用 (2015)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会第27回バイオエンジニアリング講演会
  • Place of Presentation: 新潟
  • Year and Date: 2015-01-09 – 2015-01-10
• [Presentation] 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 (2014)
  • Author(s): 長山和亮, 岩田 誠, 松本健郎
  • Organizer: 日本生物物理学会第52回年会
  • Place of Presentation: 札幌
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Analysis of the Cytoskeleton-Nucleus Mechanotransduction Pathway: Direct Force Transmission from the Actin Stress Fibers to the Nucleus (2014)
  • Author(s): K Nagayama, S Yamazaki, Y Yahiro, T Matsumoto
  • Organizer: The 4th Japan-Switzerland Workshop on Biomechanics
  • Place of Presentation: Shima, Japan
  • Year and Date: 2014-09-01 – 2014-09-05
• [Presentation] Mechanical interaction between actin stress fibers and the nucleus: Direct force transmission from the whole-cell level to the nucleus (2014)
  • Author(s): K Nagayama, Y Yahiro, S Yamazaki, T Matsumoto
  • Organizer: The 7th World Congress of Biomechanics (WBC2014)
  • Place of Presentation: Boston, MA, USA
  • Year and Date: 2014-07-06 – 2014-07-11
  • Invited
• [Presentation] Changes in the mechanical environment of nucleus during the phenotypic changes of vascular smooth muscle cells (2014)
  • Author(s): K Nagayama, M Iwata, Y Hamaji, T Matsumoto
  • Organizer: International Symposium on Mechanobiology 2014 (ISMB2014)
  • Place of Presentation: Okayama, Japan
  • Year and Date: 2014-05-20 – 2014-05-23
  • Invited
• [Presentation] Study on the Biomechanical Response of Cells using Microfabricated Tools and Optics : Intracellular Force Transmission Involved in Cellular Functions (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The 6th Workshop on Biological Applications of Plasma
  • Place of Presentation: 大阪(招待講演)
  • Year and Date: 2013-03-08
• [Presentation] 細胞の力学応答を司る細胞内構成要素の力学的相互作用 (2013)
  • Author(s): 長山和亮
  • Organizer: 細胞研究会「細胞機能究明の最前線」
  • Place of Presentation: 千葉(招待講演)
  • Year and Date: 2013-03-01
• [Presentation] 細胞核の力学環境に対するアクチンストレスファイバの役割 (2013)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会 第25回バイオエンジニアリング講演会
  • Place of Presentation: つくば
  • Year and Date: 2013-01-09
• [Presentation] n the Roles of Actin Stress Fibers on the Mechanical Regulation of Nucleus in Adherent Cells (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The 15th International Conference on Biomedical Engineering. (ICBME 2013)
  • Place of Presentation: National University of Singapore
• [Presentation] Direct application of mechanical stimuli to cell adhesion sites using magnetic-driven micropillar substrates (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The 15th International Conference on Biomedical Engineering. (ICBME 2013)
  • Place of Presentation: National University of Singapore
• [Presentation] メカノトランスダクションの解明に向けた細胞バイオメカニクス: 焦点接着斑・細胞骨格・核の力学的相互作用の解析 (2013)
  • Author(s): 長山和亮
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸
  • Invited
• [Presentation] Actin cap fibers and basal stress fibers have different roles in mechanical regulation of cell nucleus (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The 7th Asian Pacific Conference on Biomechanics (APCB2013)
  • Place of Presentation: Seoul, Korea
• [Presentation] Laser Nano-Dissection for Analysis of Cellular Mechanotransduction: Direct Force Transmission from Actin Stress Fibers to Nucleus: Tensional Homeostasis of Vascular Smooth Muscle Cells (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: the 35th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
  • Place of Presentation: 大阪
  • Invited
• [Presentation] 骨芽細胞様細胞Saos-2の石灰化過程における核内外の力学場の変化 (2013)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会 2013年度年次大会
  • Place of Presentation: 岡山
• [Presentation] On the Roles of Actin Stress Fibers on the Mechanical Environment of Nucleus in Adherent Cells (2013)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The 23^<rd> RIKEN Center for Developmental Biology (CDB) Meeting, Building multicellular systems from Cellular Cross-Talk
  • Place of Presentation: 神戸
• [Presentation] In-situ Measurement of Traction Force at Focal Adhesions during Macroscopic Stretch/Release of Vascular Smooth Muscle Cells : Tensional Homeostasis of Vascular Smooth Muscle Cells (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: BMES 2012 Annual Fall Meeting 2012
  • Place of Presentation: Georgia World Congress Center Atlanta, Georgia, USA
• [Presentation] In-Situ Measurement of Traction Force at Focal Adhesions during Macroscopic Cell Stretching Using an Elastic Micropillar Substrate : Tensional Homeostasis ofVascular Smooth Muscle Cells (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: The Ninth International Conference on Flow Dynamics
  • Place of Presentation: 仙台(招待講演)
• [Presentation] 血管平滑筋細胞内ストレスファイバの配向ならびに張力の再現機構に関する研究 (2012)
  • Author(s): 長山和亮
  • Organizer: 日本機械学会 M&M2012カンファレンス
  • Place of Presentation: 松山
• [Presentation] A novel magnetic-driven micropillar array substrate for analysis of mechanical responses of cells (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Organizer: 第51回日本生体医工学会大会
  • Place of Presentation: 福岡(招待講演)
• [Presentation] 磁気駆動マイクロピラーを用いた細胞の接着部位への直接的力学刺激負荷と張力応答解析 (2012)
  • Author(s): 井上卓哉
  • Organizer: 日本機械学会第22回バイオフロンティア講演会
  • Place of Presentation: 弘前
• [Book] Vascular Engineering (2016)
  • Author(s): Matsumoto T, Sugita S, Nagayama K
  • Total Pages: 15
  • Publisher: Springer
• [Book] 機械の研究 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～ (2015)
  • Author(s): 大橋俊朗, 長山和亮, 工藤奨
  • Total Pages: 10
  • Publisher: 養賢堂
• [Book] 「機械の研究」 (2015)
  • Author(s): 長山和亮
  • Publisher: 養賢堂
• [Book] Vascular Engineering (2015)
  • Author(s): Matsumoto T, Sugita S, Nagayama K
  • Publisher: Springer
• [Book] 細胞工学, 細胞骨格・核のメカノトランスダクションとその解析技法： アクチンストレスファイバーから核への力の伝達 (2014)
  • Author(s): 長山和亮
  • Total Pages: 102
  • Publisher: 学研メディカル秀潤社
• [Book] "On the roles of actin stress fibers on the mechanical environment of nucleus in vascular smooth muscle cells", Recent Advances in Mechanobiology, Editor-in-Chief : Shu Chien, Shi Yongde, and Masahiro Sokabe (2012)
  • Author(s): Kazuaki NAGAYAMA
  • Total Pages: 5
  • Publisher: Shanghai Scientific and Technological Literature Publishing House
• [Remarks] バイオメカニクス研究室
  • URL: http://biomech.web.nitech.ac.jp/top.html
• [Remarks] 茨城大学工学部知能システム工学科
  • URL: https://info.ibaraki.ac.jp/Profiles/27/0002641/profile.html
• [Remarks] 茨城大学知能システム工学科 長山和亮
  • URL: http://info.ibaraki.ac.jp/Profiles/27/0002641/profile.html
• [Remarks] 名古屋工業大学・大学院工学研究科・機能工学専攻 バイオメカニクス研究室
  • URL: http://biomech.web.nitech.ac.jp/top.html
• [Remarks]
  • URL: http://biomech.web.nitech.ac.jp/top.html