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bioRxiv · 10.1101/2025.11.12.688129

A tale of two distinct actin networks underlies the entire life cycle of focal adhesion

Dong, R.·ishii, K.·Plotnikov, S. V.·Liu, J.
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Abstract

Cell assembles focal adhesion (FA) to transmit the stress fiber (SF)-based actomyosin contraction onto the extracellular matrix (ECM) for mesenchymal migration, essential for many physiological processes (e.g., development and wound healing). To transmit force efficiently, both FA and SF contractility are built as "clutches" and in positive feedback with each other; conversely, the SF-engaging FA imposes a strong cell-ECM anchorage and must be disassembled timely to facilitate the cell migration. How the cell balances the two opposing roles of FA in cell migration is an open question. Particularly, it is not well-understood how a cell builds the FA de novo to clutch with SF and disassemble the clutches when needed in a coherent manner. Combining theory and experiments, we show that the entire life cycle of FA is seamlessly orchestrated by the FA-localized spatiotemporal coordination between retrograde actin flow and SF, without destroying the FA constituent molecules. Retrograde actin flow drives the centripetal growth of nascent FA, paving the way for SF engagement. The SF further stabilizes the growing FA into maturation via the positive feedback that clutches the contractility with the FA. Finally, the retrograde actin flow increase, in coupling to the local cell edge retraction, tugs the mature FA in the proximal direction that relaxes the associated SF contractility, turns off the clutching, and triggers the FA disassembly. Our finding sheds light on the organizational principles that cell streamlines the mechanochemical interplay between FA, actin cytoskeleton, and cell edge dynamics for efficient cell migration.

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Dong, R., ishii, K., Plotnikov, S. V., Liu, J.. 2025-11-13. A tale of two distinct actin networks underlies the entire life cycle of focal adhesion. https://doi.org/10.1101/2025.11.12.688129

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