Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution.

Wang, HJ; Wang, Y; Mirjavadi, SS; Andersen, T; Moldovan, L; Vatankhah, P; Russell, B; Jin, J; Zhou, Z; Li, Q; Cox, CD; Su, QP; Ju, LA

Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution.

Wang, HJ Wang, Y Mirjavadi, SS Andersen, T Moldovan, L Vatankhah, P Russell, B Jin, J Zhou, Z Li, Q Cox, CD Su, QP Ju, LA

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Publisher:: NATURE PORTFOLIO
Publication Type:: Journal Article
Citation:: Nat Commun, 2024, 15, (1), pp. 5521
Issue Date:: 2024-06-29

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Field	Value	Language
dc.contributor.author	Wang, HJ
dc.contributor.author	Wang, Y
dc.contributor.author	Mirjavadi, SS
dc.contributor.author	Andersen, T
dc.contributor.author	Moldovan, L
dc.contributor.author	Vatankhah, P
dc.contributor.author	Russell, B
dc.contributor.author	Jin, J
dc.contributor.author	Zhou, Z
dc.contributor.author	Li, Q
dc.contributor.author	Cox, CD
dc.contributor.author	Su, QP
dc.contributor.author	Ju, LA
dc.date.accessioned	2024-08-01T04:43:23Z
dc.date.available	2024-06-20
dc.date.available	2024-08-01T04:43:23Z
dc.date.issued	2024-06-29
dc.identifier.citation	Nat Commun, 2024, 15, (1), pp. 5521
dc.identifier.issn	2041-1723
dc.identifier.issn	2041-1723
dc.identifier.uri	http://hdl.handle.net/10453/179960
dc.description.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.
dc.format	Electronic
dc.language	eng
dc.publisher	NATURE PORTFOLIO
dc.relation	http://purl.org/au-research/grants/arc/DP200101970
dc.relation	http://purl.org/au-research/grants/nhmrc/1177374
dc.relation.ispartof	Nat Commun
dc.relation.isbasedon	10.1038/s41467-024-49833-6
dc.rights	info:eu-repo/semantics/restrictedAccess
dc.subject.mesh	Humans
dc.subject.mesh	Ion Channels
dc.subject.mesh	Mechanotransduction, Cellular
dc.subject.mesh	Actins
dc.subject.mesh	HEK293 Cells
dc.subject.mesh	Cytoskeleton
dc.subject.mesh	Calcium
dc.subject.mesh	Calcium Signaling
dc.subject.mesh	Finite Element Analysis
dc.subject.mesh	Animals
dc.subject.mesh	Microscopy, Fluorescence
dc.subject.mesh	Cytoskeleton
dc.subject.mesh	Animals
dc.subject.mesh	Humans
dc.subject.mesh	Calcium
dc.subject.mesh	Actins
dc.subject.mesh	Ion Channels
dc.subject.mesh	Microscopy, Fluorescence
dc.subject.mesh	Mechanotransduction, Cellular
dc.subject.mesh	Calcium Signaling
dc.subject.mesh	Finite Element Analysis
dc.subject.mesh	HEK293 Cells
dc.title	Microscale geometrical modulation of PIEZO1 mediated mechanosensing through cytoskeletal redistribution.
dc.type	Journal Article
utslib.citation.volume	15
utslib.location.activity	England
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
utslib.copyright.status	recently_added	*
dc.date.updated	2024-08-01T04:43:14Z
pubs.issue	1
pubs.publication-status	Published online
pubs.volume	15
utslib.citation.issue	1

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.

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http://hdl.handle.net/10453/179960