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Study on the effects of the mechanical environment of the cell nucleus on the radiation resistance of cells

Research Project

Project/Area Number 17H02077
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionIbaraki University

Principal Investigator

Nagayama Kazuaki  茨城大学, 理工学研究科(工学野), 教授 (10359763)

Co-Investigator(Kenkyū-buntansha) 坂元 尚哉  首都大学東京, システムデザイン研究科, 准教授 (20361115)
菅原 路子  千葉大学, 大学院工学研究院, 准教授 (30323041)
Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000)
Fiscal Year 2019: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000)
Keywords細胞バイオメカニクス / メカノバイオロジー / 細胞核 / 細胞骨格 / DNA / 細胞計測・操作
Outline of Final Research Achievements

We investigated the effects of mechanical stimulation on nuclear morphology and resistance of intracellular DNA to UV damage. Adherent cells on silicone elastic membranes were subjected to ~10% cyclic uniaxial stretch at a frequency of 0.5 Hz for 12 h. The intracellular actin cytoskeleton and nucleus were found to be elongated and aligned in an actomyosin tension-dependent manner. The nuclei of the stretched cells were dramatically compressed by the reorganized actin cytoskeleton, and a significant increase in the intranuclear DNA density was observed. Intercellular tension, as assessed with live cell atomic force microscopy imaging, also increased following exposure to cyclic stretch. The UV radiation-induced DNA damage significantly decreased in these stretched cells. These results indicate that the cyclic stretch-induced morphological changes in the nucleus improve the UV radiation resistance of cells, probably owing to the intracellular force-induced condensation of chromatin.

Academic Significance and Societal Importance of the Research Achievements

従来研究では,紫外線や放射線に暴露されたときにDNAが修復する分子メカニズムに注目した生化学的研究が多かった.これに対し,本研究では,より重要と考えられる「紫外線や放射線からDNAを効果的に守る手法」の開発に着目し,細胞への力学刺激が効果的な方法の1つであることを世界で初めて見出した.

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (50 results)

All 2020 2019 2018 2017 Other

All Journal Article (13 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 13 results,  Open Access: 7 results) Presentation (31 results) (of which Int'l Joint Research: 8 results) Remarks (6 results)

  • [Journal Article] A Facile Assay of Epithelial-mesenchymal Transition Based on Cooperativity Quantification of Cellular Autonomous Motions2020

    • Author(s)
      YAMAMOTO Shota、MIYAMA Tatsuya、KOMODA Takafumi、SUGAWARA Michiko、NONOMURA Makiko、NAKANISHI Jun
    • Journal Title

      Analytical Sciences

      Volume: 36 Issue: 2 Pages: 263-268

    • DOI

      10.2116/analsci.19P233

    • NAID

      130007796068

    • ISSN
      0910-6340, 1348-2246
    • Year and Date
      2020-02-10
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Matrix mechanotransduction mediated by thrombospondin-1/integrin/YAP in the vascular remodeling2020

    • Author(s)
      Yamashiro Yoshito、Thang Bui Quoc、Ramirez Karina、Shin Seung Jae、Kohata Tomohiro、Ohata Shigeaki、Nguyen Tram Anh Vu、Ohtsuki Sumio、Nagayama Kazuaki、Yanagisawa Hiromi
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 117 Issue: 18 Pages: 9896-9905

    • DOI

      10.1073/pnas.1919702117

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cyclic stretch-induced mechanical stress to the cell nucleus inhibits ultraviolet radiationinduced DNA damage2020

    • Author(s)
      Nagayama Kazuaki, Fukuei Tomohiro
    • Journal Title

      Biomechanics and Modeling in Mechanobiology 493

      Volume: 19 Issue: 2 Pages: 493-504

    • DOI

      10.1007/s10237-019-01224-3

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mechanical Stress to Cell Nucleus Inhibits Proliferation and Differentiation of Vascular Smooth Muscle Cells2020

    • Author(s)
      Nagayama Kazuaki
    • Journal Title

      Journal of Biosciences and Medicines

      Volume: 08 Issue: 05 Pages: 132-141

    • DOI

      10.4236/jbm.2020.85013

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a Cell Micro Tensile Tester and Its Application to Quantitative Analysis of Cell Stiffness and Adhesion Forces of Vascular Smooth Muscle Cells2019

    • Author(s)
      Nagayama Kazuaki、Ohata Shigeaki
    • Journal Title

      Journal of the Japan Society for Precision Engineering

      Volume: 85 Issue: 9 Pages: 800-804

    • DOI

      10.2493/jjspe.85.800

    • NAID

      130007702944

    • ISSN
      0912-0289, 1882-675X
    • Year and Date
      2019-09-05
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Biomechanical analysis of the mechanical environment of the cell nucleus in serum starvation-induced vascular smooth muscle cell differentiation2019

    • Author(s)
      NAGAYAMA Kazuaki
    • Journal Title

      Journal of Biomechanical Science and Engineering

      Volume: 14 Issue: 4 Pages: 19-00364-19-00364

    • DOI

      10.1299/jbse.19-00364

    • NAID

      130007775702

    • ISSN
      1880-9863
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Directional Dependence of Cyclic Stretch-induced Cell Migration in Wound Healing Process of Monolayer Cells2019

    • Author(s)
      Nagayama Kazuaki、Suzuki Yuya、Fujiwara Daisuke
    • Journal Title

      Advanced Biomedical Engineering

      Volume: 8 Issue: 0 Pages: 163-169

    • DOI

      10.14326/abe.8.163

    • NAID

      130007732059

    • ISSN
      2187-5219
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel micro-grooved collagen substrate for inducing vascular smooth muscle differentiation through cell tissue arrangement and nucleus remodeling2018

    • Author(s)
      Nagayama Kazuaki, Uchida Keiichi, Sato Aiko.
    • Journal Title

      Journal of the Mechanical Behavior of Biomedical Materials

      Volume: 90 Pages: 295-305

    • DOI

      10.1016/j.jmbbm.2018.10.005

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct application of mechanical stimulation to cell adhesion sites using a novel magnetic-driven micropillar substrate2018

    • Author(s)
      Nagayama K, Inoue T, Hamada Y, Sugita S, Matsumoto T
    • Journal Title

      Biomed Microdevices

      Volume: 20 Issue: 4 Pages: 85-85

    • DOI

      10.1007/s10544-018-0328-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The effects of substrate stiffness on the morphology, intercellular tension, and differentiation of vascular smooth muscle cells (Analysis of the surface microstructure and tension of cells using atomic force microscopy)2018

    • Author(s)
      長山和亮,西宮昂平
    • Journal Title

      Transactions of the JSME (in Japanese)

      Volume: 84 Issue: 868 Pages: 18-00387-18-00387

    • DOI

      10.1299/transjsme.18-00387

    • NAID

      130007550594

    • ISSN
      2187-9761
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Finite Element Bendo-Tensegrity Model of Eukaryotic Cell2018

    • Author(s)
      Bansod Yogesh Deepak、Matsumoto Takeo、Nagayama Kazuaki、Bursa Jiri
    • Journal Title

      Journal of Biomechanical Engineering

      Volume: 140 Issue: 10 Pages: 101001-101001

    • DOI

      10.1115/1.4040246

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A novel patterned magnetic micropillar array substrate for analysis of cellular mechanical responses2017

    • Author(s)
      Nagayama Kazuaki、Inoue Takuya、Hamada Yasuhiro、Matsumoto Takeo
    • Journal Title

      Journal of Biomechanics

      Volume: 65 Pages: 194-202

    • DOI

      10.1016/j.jbiomech.2017.10.017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Effects of cyclic compression on the mechanical properties and calcification process of immature chick bone tissue in culture2017

    • Author(s)
      Maeda Eijiro、Nakagaki Masashi、Ichikawa Katsuhisa、Nagayama Kazuaki、Matsumoto Takeo
    • Journal Title

      Bone Reports

      Volume: 6 Pages: 120-128

    • DOI

      10.1016/j.bonr.2017.04.002

    • NAID

      120006331843

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 形状極性を有する細胞における骨格および小器官の分布に関する研究2019

    • Author(s)
      小祝穂高, 山口和夫, 中西淳, 菅原路子
    • 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] マイクロパターン形成手法を用いた細胞形状の違いによる細胞内小器官の三次元配置解析2019

    • Author(s)
      小祝穂高,瀧上颯太,吉田一樹,山口和夫,中西淳,菅原路子
    • Organizer
      日本機械学会第25期総会・講演会
    • Related Report
      2019 Annual Research Report
  • [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] 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] 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] 酸性ストレスが細胞周期および細胞運動に与える影響2019

    • Author(s)
      佐々木達也,長山和亮
    • 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] 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2019

    • Author(s)
      三浦光騎,長山和亮
    • Organizer
      日本機械学会2019年度年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      長山和亮
    • Organizer
      日本機械学会2019年度年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      小幡祥太,長山和亮
    • Organizer
      日本機械学会2019年度年次大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      村田博教,長山和亮
    • Organizer
      第30回バイオフロンティア講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      半沢達也,長山和亮
    • Organizer
      第30回バイオフロンティア講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      野上謙三,長山和亮
    • Organizer
      第30回バイオフロンティア講演会
    • Related Report
      2019 Annual Research Report
  • [Presentation] A novel micro-grooved collagen substrate for inducing vascular smooth muscle cell differentiation through cell tissue arrangement and nucleus remodeling2019

    • Author(s)
      Nagayama K
    • Organizer
      10th Asian-Pacific Conference on Biomechanics (AP Biomech 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Cyclic stretch-induced mechanical stress to the cell nucleus improves the ultraviolet radiation resistance in cells2019

    • Author(s)
      Nagayama K, Fukuei T
    • Organizer
      The 17th International Conference on Biomedical Engineering (ICBME2019)
    • Related Report
      2019 Annual Research Report
  • [Presentation] 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2019

    • Author(s)
      長山和亮
    • Organizer
      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」
    • Related Report
      2018 Annual Research Report
  • [Presentation] 細胞形状拘束下における微小管および細胞内小器官の分布に関する研究2019

    • Author(s)
      菅原路子
    • 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] Analysis of collective cell migration on geometrically constrained circular region using Particle Image Velocimetry2019

    • Author(s)
      Sugawara Michiko
    • Organizer
      The 3rd International Symposium on Nanoarchitectonics for Mechanobiology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Nuclear-cytoskeletal Interactions in Vascular Smooth Muscle Cells:Possible Roles in the Regulation of Cell Differentiation,2018

    • Author(s)
      Nagayama Kazuaki
    • Organizer
      8th World Congress of Biomechanics (WCB2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Investigation of the nuclear-cytoskeletal interactions in vascular smooth muscle cell differentiationusing a novel micro-grooved collagen substrate2018

    • Author(s)
      Nagayama Kazuaki
    • Organizer
      8th World Congress of Biomechanics (WCB2018)
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 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2018

    • Author(s)
      長山和亮
    • Organizer
      日本機械学会2018年度 年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 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2018

    • Author(s)
      長山和亮
    • Organizer
      日本機械学会2018年度 年次大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 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2018

    • Author(s)
      佐々木達也,長山和亮
    • Organizer
      第29回日本機械学会バイオフロンティア講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 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バと核の結合状態の推察2018

    • Author(s)
      大畠成暁,長山和亮
    • 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] 血管平滑筋分化における核内外の力学環境の変化2018

    • Author(s)
      長山和亮,佐藤亜希子
    • 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] Investigation of the nuclear cytoskeletal interactions in vascular smooth muscle cells cultured on a micro-grooved collagen substrate,the 5th Switzerland-Japan Workshop on Biomechanics.2017

    • Author(s)
      Nagayama Kazuaki, Uchida Keiichi, Takeuchi Saki
    • Organizer
      the 5th Switzerland-Japan Workshop on Biomechanics
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] The biomechanical effects of the deformation and trapping of the nucleus on cellular UV resistance.2017

    • Author(s)
      Nagayama Kazuaki, Sagawa Chiaki
    • Organizer
      XXVI Congress of the International Society of Biomechanics (ISB2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 細胞核の力学場が細胞紫外線耐性に与える影響,2017

    • Author(s)
      長山和亮,佐川千秋
    • Organizer
      第56回日本生体医工学会大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 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,2017

    • Author(s)
      長山和亮
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 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,2017

    • Author(s)
      長山和亮,内田敬一, 竹内 早希
    • Organizer
      日本機械学会2017年度年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 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~2017

    • Author(s)
      佐川千秋,長山和亮
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 繰返引張刺激による細胞の紫外線耐性向上の可能性2017

    • Author(s)
      福栄智大,長山和亮
    • Organizer
      日本機械学会第30回バイオエンジニアリング講演会
    • Related Report
      2017 Annual Research Report
  • [Remarks] 茨城大学研究者情報(長山和亮)

    • URL

      https://info.ibaraki.ac.jp/Profiles/27/0002641/profile.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 茨城大学 マイクロ・ナノバイオメカニクス研究室(長山研)ホームページ

    • URL

      http://biomech.mechsys.ibaraki.ac.jp/index.html

    • Related Report
      2019 Annual Research Report
  • [Remarks] 東京都立大学 メカノバイオロジー研究室(坂元研)ホームページ

    • URL

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

    • Related Report
      2019 Annual Research Report
  • [Remarks] 千葉大学 細胞システム工学研究室(菅原研)ホームページ

    • URL

      https://sites.google.com/site/msugawara2011/

    • Related Report
      2019 Annual Research Report
  • [Remarks] 茨城大学理工学研究科(工学野)研究者情報 長山和亮

    • URL

      https://info.ibaraki.ac.jp/Profiles/27/0002641/profile.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] 茨城大学理工学研究科(工学野)研究者情報 長山和亮

    • URL

      http://info.ibaraki.ac.jp/Profiles/27/0002641/profile.html

    • Related Report
      2017 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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