| Project/Area Number |
18H03510
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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 | The University of Tokyo |
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Principal Investigator |
Yamamoto Kimiko 東京大学, 大学院医学系研究科(医学部), 准教授 (00323618)
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| Co-Investigator(Kenkyū-buntansha) |
安藤 譲二 獨協医科大学, 医学部, 特任教授 (20159528)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2020: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
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| Keywords | 血管内皮細胞 / Shear stress / 形質膜 / リン脂質 / コレステロール |
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| Outline of Final Research Achievements |
The function of vascular endothelial cells is regulated by the shear stress caused by blood flow. However, it is unclear how endothelial cells sense shear stress. In this study, we aimed to elucidate the mechanical response of the plasma membrane itself, which is a phospholipid bilayer, from a new perspective. We established a new method for live imaging of cholesterol molecules in cell membranes and found that shear stress instantly reduces cholesterol in the plasma membrane. Biochemical quantitative analysis showed that the amount of cholesterol was reduced by about 60% compared to the control under static conditions. Furthermore, it was found that shear stress-induced cholesterol reduction played an important role in shear stress-dependent calcium signaling.
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| Academic Significance and Societal Importance of the Research Achievements |
剪断応力で多くの膜分子がほぼ同時に活性化する機序として、細胞膜の物理的性質（脂質相転移や流動性）や、膜を構成する脂質分子の変化が関与することが明らかとなった。すなわち、本研究成果により、細胞膜自体がメカノセンサーとして働く可能性を示した。血流センシングの仕組みを生細胞膜と類似した人工脂質二重膜のリポソームを使って解析する各種のライブイメージング技術を駆使した生物物理的実験を通して、細胞の応答を物理現象とし捉えることで、血管以外の力学的刺激が作用する細胞や組織に共通のメカノセンシング機構が明らかとなった。
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