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Study on the role of the mechanical dynamics in the nucleus in cellular mechanical responses

Research Project

Project/Area Number 18H03521
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 90110:Biomedical engineering-related
Research InstitutionTokyo Metropolitan University

Principal Investigator

SAKAMOTO NAOYA  東京都立大学, システムデザイン研究科, 准教授 (20361115)

Co-Investigator(Kenkyū-buntansha) 三好 洋美  東京都立大学, システムデザイン研究科, 准教授 (50455367)
伊井 仁志  東京都立大学, システムデザイン研究科, 准教授 (50513016)
Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Keywords細胞核 / アクチン細胞骨格 / クロマチン / 不均質性 / LINC複合体 / メカノバイオロジー / 細胞バイオメカニクス / 細胞骨格 / 細胞内張力 / 架橋タンパク質 / 転写活性
Outline of Final Research Achievements

The nuclear deformation and strain caused by the mechanical forces transmitted from outside of the cell to the nucleus via cytoskeletons can affect the accessibility of mechanosensitive transcription factors and ultimately gene expression. Thus, understanding nuclear mechanical properties and deformation against mechanical stimuli is the key to revealing how nuclear mechanics controls the biochemical activity. In this study, we explored intranuclear mechanical properties and the mechanical relationship between the nucleus and cellular traction forces. As a result, we found a heterogenous distribution of mechanical properties in the nucleus, which is thought to be determined by intranuclear structure components other than DNA condensation states. Our results also suggest that the nucleus play an important role in intracellular distributions of actin cytoskeletons and traction forces.

Academic Significance and Societal Importance of the Research Achievements

力学環境に対する細胞応答は身体の生理機能維持や病理に深く関与することが知られている.細胞の力学環境への応答メカニズムにおいて,細胞外部の力学環境情報の細胞核への伝達および細胞核の変形が重要な役割を担うとして注目されている.力学特性は変形に極めて密接にかかわる物性であり,本研究結果は,伝達された力が,細胞核内部で局所的に異なる変形を引き起こし,細胞核内部のDNA構造等を変化させることで細胞応答を導く可能性を示唆する.また細胞核の存在も,力の伝達に重要な細胞骨格構造に影響を与える相互作用を持つことを示し,細胞応答メカニズムの解明に大きく寄与すると考えられる.

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • Research Products

    (30 results)

All 2021 2020 2019 2018 Other

All Int'l Joint Research (6 results) Journal Article (2 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (20 results) (of which Int'l Joint Research: 9 results,  Invited: 1 results) Remarks (2 results)

  • [Int'l Joint Research] Virginia Commonwealth University/University of California, Berkeley(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] シンガポール科学技術研究庁バイオ情報研究所(シンガポール)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Virginia Commonwealth University/University of California, Berkeley(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] シンガポール科学技術研究庁バイオ情報研究所(シンガポール)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] Virginia Commonwealth University(米国)

    • Related Report
      2018 Annual Research Report
  • [Int'l Joint Research] シンガポール科学技術研究庁バイオ情報研究所(シンガポール)

    • Related Report
      2018 Annual Research Report
  • [Journal Article] A 3D tissue model-on-a-chip for studying the effects of human senescent fibroblasts on blood vessels2021

    • Author(s)
      Pauty Joris、Nakano Shizuka、Usuba Ryo、Nakajima Tadaaki、Johmura Yoshikazu、Omori Satotaka、Sakamoto Naoya、Kikuchi Akihiko、Nakanishi Makoto、Matsunaga Yukiko T.
    • Journal Title

      Biomaterials Science

      Volume: 9 Issue: 1 Pages: 199-211

    • DOI

      10.1039/d0bm01297a

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intranuclear strain in living cells subjected to substrate stretching: A combined experimental and computational study2021

    • Author(s)
      Tsukamoto Shingo、Asakawa Takumi、Kimura Shun、Takesue Naoyuki、Mofrad Mohammad R.K.、Sakamoto Naoya
    • Journal Title

      Journal of Biomechanics

      Volume: 119 Pages: 110292-110292

    • DOI

      10.1016/j.jbiomech.2021.110292

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] 高浸透圧刺激による尿細管細胞の細胞骨格構造の変化が腎線維化に与える影響2020

    • Author(s)
      宮野貴士,鈴木敦詞,坂元尚哉
    • Organizer
      第59回日本生体医工学会大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Quantitative analysis of nuclear local viscoelastic changes in human Mesenchymal Stem Cells during osteoblast differentiation2020

    • Author(s)
      K. Matsushita, N. Sakamoto, S. Ii, H. Miyoshi
    • Organizer
      Summer Biomechanics, Bioengineering and Biotransport Conference 2020
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Intranuclear mechanics under cell substrate stretching: AN experimental and computational study2020

    • Author(s)
      S. Tsukamoto, S. Kimura, T. Asakawa, N. Takesue, M.R.K. Mofrad, N. Sakamoto
    • Organizer
      Intranuclear mechanics under cell substrate stretching: AN experimental and computational study
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 高浸透圧条件下における尿細管細胞内カルシウムイオン濃度変化2020

    • Author(s)
      鈴木敦詞,宮野貴士,坂元尚哉
    • Organizer
      日本機械学会第31回バイオフロンティア講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] ヒト間葉系幹細胞の細胞核内粘弾性変化の骨芽細胞分化における役割2020

    • Author(s)
      松下 晃次郎,坂元 尚哉,伊井 仁志,三好 洋美
    • Organizer
      日本機械学会2020年度年次大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 細胞核変形の細胞外基質伸展方向との関係2020

    • Author(s)
      塚本真悟,Keng-Hwee Chaim,武居直行,坂元尚哉
    • Organizer
      日本機械学会第31回バイオフロンティア講演会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Effects of the hyperosmolarity-induced cytoskeletal changes of tubule epithelial cells on renal fibrosis2020

    • Author(s)
      T. Miyano, A. Suzuki, N. Sakamoto
    • Organizer
      TMU International Symposium: Multi-scale biomechanics, nano-to macro-scale
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 接着基質力学特性の違いによって引き起こされる細胞内張力の変化2019

    • Author(s)
      伊藤佳祐,伊井仁志,Daniel Conway,坂元尚哉
    • Organizer
      日本機械学会第32回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 圧縮コラーゲン組織を用いた共培養モデルに対する高壁せん断応力の影響2019

    • Author(s)
      大山侑樹,中村匡徳,木村直行,川人宏次,山崎雅史,藤江裕道,坂元尚哉
    • Organizer
      日本機械学会第32回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 間葉系幹細胞の内皮細胞分化効率向上を目指した組合せ力学環境の検討2019

    • Author(s)
      舘林耕平 三好洋美 山崎雅史 坂元尚哉
    • Organizer
      日本機械学会第32回バイオエンジニアリング講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Heterogeneous strain distribution within the nucleus under substrate stretching is caused by chromatin condensation2019

    • Author(s)
      S. Tukamoto, S. Kimura, N. Takesue, N. Sakamoto
    • Organizer
      2019 BMES Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Roles of nuclear membrane proteins in cyclic stretch-induced changes of nuclear elasticity of fibroblasts2019

    • Author(s)
      N. Sakamoto, K. Kashima, M. Takeuchi, N. Kataoka
    • Organizer
      2019 BMES Annual Meeting
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Inverse Estimation of 3-D Traction Stress Field of Adhered Cell based on Optimal Control Technique using Image Intensities2019

    • Author(s)
      S. Ii, K. Ito, N. Takakusaki, N. Sakamoto
    • Organizer
      International Conference on Biomehanics and Medical Engineering
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] ヒト間葉系幹細胞の骨分化過程における細胞核内局所粘弾性の定量評価2019

    • Author(s)
      松下 晃次郎,坂元 尚哉,伊井 仁志,三好 洋美
    • Organizer
      日本機械学会2019年度年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Condensation Level of Chromatin Affects Local Strain within the Nucleus under Mechanical Stimuli2019

    • Author(s)
      S. Tsukamoto, S., Kimura, N. Takesue, N. Sakamoto
    • Organizer
      3rd International Symposium on Nanoarchitectonics for Mechanobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Matrix metalloproteinase production of vascular endothelial cells under extremely high wall shear stress condition. The International Society of Biorheology2018

    • Author(s)
      N. Sakamoto, Y. Oyama, Y. Horie, M. Nakamura, N. Kimura
    • Organizer
      The International Society of Biorheology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Mechanical conditions of nesprin-mediated nucleus-actin filament bindings affect polarized elongation of fibroblasts induced by cyclic stretching2018

    • Author(s)
      N. Sakamoto, M. Ogawa, K. Sadamoto, M. Takeuchi, N. Kataoka
    • Organizer
      8th World Congress of Biomechanics
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] パーティクルトラッキング法による細胞核内局所力学特性の評価2018

    • Author(s)
      木村 俊,三好 洋美,伊井 仁志,坂元 尚哉
    • Organizer
      日本機械学会第29回バイオフロンティア講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 血管内皮細胞の遊走および剥離に対する衝突流れ場の影響2018

    • Author(s)
      堀江悠太,大山侑樹,中村匡徳,木村直行,川人宏次,坂元尚哉
    • Organizer
      日本機械学会第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 繰り返し伸展刺激による繊維芽細胞核の弾性特性変化における核膜タンパク質の役割2018

    • Author(s)
      香嶋 謙志郎,竹内 雅貴,片岡 則之,坂元 尚哉
    • Organizer
      日本機械学会第31回バイオエンジニアリング講演会
    • Related Report
      2018 Annual Research Report
  • [Remarks] Mechanobiology Laboratoryのホームページ

    • URL

      http://www.comp.sd.tmu.ac.jp/mechanobio/index.html

    • Related Report
      2020 Annual Research Report 2019 Annual Research Report
  • [Remarks] Mechanobiology Laboratoryのホームページ

    • URL

      https://sites.google.com/site/sakamotonlab/

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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