Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair
Date
2021-04-21
Authors
Zhou, Dennis W.
Fernández-Yagüe, Marc A.
Holland, Elijah N.
García, Andres F.
Castro, Nicolas S.
O'Neill, Eric B.
Eyckmans, Jeroen
Chen, Christopher S.
Fu, Jianping
Schlaepfer, David D.
Version
Published version
OA Version
Citation
D.W. Zhou, M.A. Fernández-Yagüe, E.N. Holland, A.F. García, N.S. Castro, E.B. O'Neill, J. Eyckmans, C.S. Chen, J. Fu, D.D. Schlaepfer, A.J. García. 2021. "Force-FAK signaling coupling at individual focal adhesions coordinates mechanosensing and microtissue repair.." Nat Commun, Volume 12, Issue 1, pp. 2359 - ?. https://doi.org/10.1038/s41467-021-22602-5
Abstract
How adhesive forces are transduced and integrated into biochemical signals at focal adhesions (FAs) is poorly understood. Using cells adhering to deformable micropillar arrays, we demonstrate that traction force and FAK localization as well as traction force and Y397-FAK phosphorylation are linearly coupled at individual FAs on stiff, but not soft, substrates. Similarly, FAK phosphorylation increases linearly with external forces applied to FAs using magnetic beads. This mechanosignaling coupling requires actomyosin contractility, talin-FAK binding, and full-length vinculin that binds talin and actin. Using an in vitro 3D biomimetic wound healing model, we show that force-FAK signaling coupling coordinates cell migration and tissue-scale forces to promote microtissue repair. A simple kinetic binding model of talin-FAK interactions under force can recapitulate the experimental observations. This study provides insights on how talin and vinculin convert forces into FAK signaling events regulating cell migration and tissue repair.
Description
License
© The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.