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

2019 Fiscal Year Final Research Report

• Project/Area Number: 17H02077
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: Ibaraki 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
• 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

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.

Free Research Field

細胞バイオメカニクス

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．