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Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution

Author

Listed:
  • Haoqing Jerry Wang

    (The University of Sydney
    The University of Sydney
    Camperdown)

  • Yao Wang

    (The University of Sydney)

  • Seyed Sajad Mirjavadi

    (The University of Sydney)

  • Tomas Andersen

    (The University of Sydney)

  • Laura Moldovan

    (The University of Sydney
    The University of Sydney
    Camperdown)

  • Parham Vatankhah

    (The University of Sydney)

  • Blake Russell

    (The University of Sydney)

  • Jasmine Jin

    (The University of Sydney)

  • Zijing Zhou

    (Victor Chang Cardiac Research Institute)

  • Qing Li

    (The University of Sydney)

  • Charles D. Cox

    (Victor Chang Cardiac Research Institute
    University of New South Wale)

  • Qian Peter Su

    (Camperdown
    University of Technology Sydney)

  • Lining Arnold Ju

    (The University of Sydney
    The University of Sydney
    Camperdown
    The University of Sydney)

Abstract

The microgeometry of the cellular microenvironment profoundly impacts cellular behaviors, yet the link between it and the ubiquitously expressed mechanosensitive ion channel PIEZO1 remains unclear. Herein, we describe a fluorescent micropipette aspiration assay that allows for simultaneous visualization of intracellular calcium dynamics and cytoskeletal architecture in real-time, under varied micropipette geometries. By integrating elastic shell finite element analysis with fluorescent lifetime imaging microscopy and employing PIEZO1-specific transgenic red blood cells and HEK cell lines, we demonstrate a direct correlation between the microscale geometry of aspiration and PIEZO1-mediated calcium signaling. We reveal that increased micropipette tip angles and physical constrictions lead to a significant reorganization of F-actin, accumulation at the aspirated cell neck, and subsequently amplify the tension stress at the dome of the cell to induce more PIEZO1’s activity. Disruption of the F-actin network or inhibition of its mobility leads to a notable decline in PIEZO1 mediated calcium influx, underscoring its critical role in cellular mechanosensing amidst geometrical constraints.

Suggested Citation

  • Haoqing Jerry Wang & Yao Wang & Seyed Sajad Mirjavadi & Tomas Andersen & Laura Moldovan & Parham Vatankhah & Blake Russell & Jasmine Jin & Zijing Zhou & Qing Li & Charles D. Cox & Qian Peter Su & Lini, 2024. "Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-49833-6
    DOI: 10.1038/s41467-024-49833-6
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    References listed on IDEAS

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