Wang, Haoqing Jerry and Wang, Yao and Mirjavadi, Seyed Sajad and Andersen, Tomas and Moldovan, Laura and Vatankhah, Parham and Russell, Blake and Jin, Jasmine and Zhou, Zijing and Li, Qing and Cox, Charles D. and Su, Qian Peter and Ju, Lining Arnold (2024) Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution. Nature Communications, 15 (1). ISSN 2041-1723
Full text not available from this repository.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.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 25 Dec 2024 23:01 |
| Last Modified: | 25 Dec 2024 23:01 |
| URI: | https://eprints.victorchang.edu.au/id/eprint/1573 |
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