2023 Fiscal Year Final Research Report
Investigation on the homeostasis mechanism of cells based on the nucleus-cytoskeleton connections
| Project/Area Number |
21H03804
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Basic Section 90110:Biomedical engineering-related
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| Research Institution | Ibaraki University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
上杉 薫 茨城大学, 理工学研究科(工学野), 助教 (20737027)
山城 義人 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (70751923)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| 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 |
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| Outline of Final Research Achievements |
To elucidate the mechanism of vascular smooth muscle cell (VSMC) homeostasis, we developed a novel micro-grooved collagen substrate to control cell orientation similar to that in aortic walls, and found that the contractile differentiation of VSMCs were significantly facilitated on this substrate. We also investigated the internal tension of actin stress fibers and the mechanical properties of the nucleus in VSMCs using atomic force microscopy, and found that nuclear stiffening and the loss of nuclear-cytoskeletal connection may be important factors not only in the maintenance of the VSMC contractile phenotype but also in the protection of biomechanical and physiological integrity of the cell nucleus from external mechanical disturbances.
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| Free Research Field |
細胞バイオメカニクス
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| Academic Significance and Societal Importance of the Research Achievements |
本課題研究で得られた成果は，細胞外の力が細胞骨格を伝わって，遺伝子を保存する核に伝達されることを実験的に証明した研究である．そして，細胞骨格と核の繋がりが，細胞の分化過程で大きく変化することを明らかにし，この繋がりによって細胞への物理的刺激による遺伝子発現感度が決定される可能性を示したものである．今後，それぞれの細胞骨格分子と核をつなぐリンカー分子の選択的操作による創薬技術への展開などが期待できる．また，開発したコラーゲン製の微細溝基質は，血管平滑筋細胞に限らず様々な細胞を用いた人工組織形成用の基材として実用可能性が大きい技術である．
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