Scholz, J., Stephan, T., Pérez, A.G. et al. (17 more authors) (2024) Decisive role of mDia-family formins in cell cortex function of highly adherent cells. Science Advances, 10 (44). eadp5929. p. 9. ISSN 2375-2548
Abstract
Cortical formins, pivotal for the assembly of linear actin filaments beneath the membrane, exert only minor effects on unconfined cell migration of weakly and moderately adherent cells. However, their impact on migration and mechanostability of highly adherent cells remains poorly understood. Here, we demonstrate that loss of cortical actin filaments generated by the formins mDia1 and mDia3 drastically compromises cell migration and mechanics in highly adherent fibroblasts. Biophysical analysis of the mechanical properties of the mutant cells revealed a markedly softened cell cortex in the poorly adherent state. Unexpectedly, in the highly adherent state, associated with a hyperstretched morphology with exaggerated focal adhesions and prominent high-strain stress fibers, they exhibited even higher cortical tension compared to control. Notably, misguidance of intracellular forces, frequently accompanied by stress-fiber rupture, culminated in the formation of tension- and contractility-induced macroapertures, which was instantly followed by excessive lamellipodial protrusion at the periphery, providing critical insights into mechanotransduction of mechanically stressed and highly adherent cells.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2024 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Biological Sciences (Leeds) > School of Molecular and Cellular Biology (Leeds) > Cell Biology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Nov 2024 16:32 |
Last Modified: | 18 Nov 2024 16:32 |
Status: | Published |
Publisher: | American Association for the Advancement of Science |
Identification Number: | 10.1126/sciadv.adp5929 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:219728 |