| Project/Area Number |
20H03218
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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 43040:Biophysics-related
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| Research Institution | Kanazawa University |
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Principal Investigator |
Franz Clemens 金沢大学, ナノ生命科学研究所, 准教授 (50837664)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2023)
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| Budget Amount *help |
¥18,070,000 (Direct Cost: ¥13,900,000、Indirect Cost: ¥4,170,000)
Fiscal Year 2022: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2021: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
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| Keywords | AFM / SICM / myosin / actin / stress fiber / contractility / HS-AFM / Myosin / Actin / High-speed AFM / Bioimaging / SPM / cytoskeleton / Stress Fibers |
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| Outline of Research at the Start |
This research projects investigates the structure and function of contractile stress fibers, which have been compared to intracellular "muscles". Understanding how these structures contract will help us to better understand how cell can move, change shape, or divide.
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| Outline of Final Research Achievements |
By combining cell de-roofing and HS-AFM imaging, this project established a method to image contracting actin stress fibers (SFs) to near molecular resolution within native cellular environments. Achieving these goals required (1) the development of suitable de-roofing methods, (2) establishment of an ultrawide scanner system for large resolution HS-AFM imaging in combination with fluorescence microscopy, and (3) developing an optimized AFM tip design for imaging highly corrugated intracellular structures. Ultrawide HS-AFM scanning generated the first molecular-resolution maps of entire native SFs, providing novel insight into SF ultrastructure. Furthermore, arrangement and conformational changes of individual non-muscle myosin II motors during SF contraction could be visualized for the first time. In parallel, SICM imaging was also adapted for intracellular imaging in de-roofed cells for the first time, providing additional structural and mechanical insight into SF contraction.
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| Academic Significance and Societal Importance of the Research Achievements |
アクチンストレスファイバー（SF）の収縮は、マトリックス接着、遊走、メカノセンシングなど、多くの細胞プロセスに影響を与える一方、SF機能の誤制御は、アテローム性動脈硬化症、骨粗鬆症、がんなどの疾患の原因となりうる。このプロジェクトで得られたSFの超微細構造とSF収縮を駆動する分子メカニズムに関する新たな知見は、SFの正常および異常機能についての理解を広げるものである。
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