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Article

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Accepted version

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2016-05

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Please use this identifier to cite or link to this item: https://hdl.handle.net/2445/155230

Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity

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https://doi.org/10.1038/ncb3336

Abstract

Cell function depends on tissue rigidity, which cells probe by applying and transmitting forces to their extracellular matrix, and then transducing them into biochemical signals. Here we show that in response to matrix rigidity and density, force transmission and transduction are explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. We demonstrate that force transmission is regulated by a dynamic clutch mechanism, which unveils its fundamental biphasic force/rigidity relationship on talin depletion. Force transduction is triggered by talin unfolding above a stiffness threshold. Below this threshold, integrins unbind and release force before talin can unfold. Above the threshold, talin unfolds and binds to vinculin, leading to adhesion growth and YAP nuclear translocation. Matrix density, myosin contractility, integrin ligation and talin mechanical stability differently and nonlinearly regulate both force transmission and the transduction threshold. In all cases, coupling of talin unfolding dynamics to a theoretical clutch model quantitatively predicts cell response.

Subject

Biologia molecular, Transducció de senyal cel·lular, Metabolisme cel·lular

Subject (English)

Molecular biology, Cellular signal transduction, Cell metabolism

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Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Publicacions de projectes de recerca finançats per la UE

Citation

ELOSEGUI ARTOLA, Alberto, et al. Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity. Nature Cell Biology. 2016. Vol. 18, num. 5, pags. 540-548. ISSN 1465-7392. [consulted: 18 of August of 2026]. Available at: https://hdl.handle.net/2445/155230

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