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Title: Mechanical regulation of a molecular clutch defines force transmission and transduction in response to matrix rigidity
Author: Elosegui Artola, Alberto
Oria, Roger
Chen, Yunfeng
Kosmalska, Anita Joanna
Pérez González, Carlos
Castro, Natalia
Zhu, Cheng
Trepat Guixer, Xavier
Roca-Cusachs Soulere, Pere
Keywords: Biologia molecular
Transducció de senyal cel·lular
Metabolisme cel·lular
Molecular biology
Cellular signal transduction
Cell metabolism
Issue Date: May-2016
Publisher: Nature Publishing Group
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.
Note: Versió postprint del document publicat a:
It is part of: Nature Cell Biology, 2016, vol. 18, num. 5, p. 540-548
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ISSN: 1465-7392
Appears in Collections:Articles publicats en revistes (Biomedicina)
Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))
Publicacions de projectes de recerca finançats per la UE

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