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Fibronectin-bound α5β1 integrins sense load and signal to reinforce adhesion in less than a second.
Journal article

Fibronectin-bound α5β1 integrins sense load and signal to reinforce adhesion in less than a second.

  • Strohmeyer N Eidgenössische Technische Hochschule (ETH) Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
  • Bharadwaj M Eidgenössische Technische Hochschule (ETH) Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
  • Costell M Department of Biochemistry and Molecular Biology, Estructura de Reserca Interdisciplinar en Biotechnologia i Biomedicina, Universitat de València, 46100 Burjassot, Spain.
  • Fässler R Max Planck Institute of Biochemistry, Department of Molecular Medicine, 82152 Martinsried, Germany.
  • Müller DJ Eidgenössische Technische Hochschule (ETH) Zürich, Department of Biosystems Science and Engineering, 4058 Basel, Switzerland.
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  • 2017-11-09
Published in:
  • Nature materials. - 2017
Actin-Related Protein 2-3 Complex
Animals
CSK Tyrosine-Protein Kinase
Cell Adhesion
Fibroblasts
Fibronectins
Focal Adhesion Kinase 1
Integrin alpha5beta1
Mechanotransduction, Cellular
Mice
Mice, Knockout
Talin
Time Factors
src-Family Kinases
English Integrin-mediated mechanosensing of the extracellular environment allows cells to control adhesion and signalling. Whether cells sense and respond to force immediately upon ligand-binding is unknown. Here, we report that during adhesion initiation, fibroblasts respond to mechanical load by strengthening integrin-mediated adhesion to fibronectin (FN) in a biphasic manner. In the first phase, which depends on talin and kindlin as well as on the actin nucleators Arp2/3 and mDia, FN-engaged α5β1 integrins activate focal adhesion kinase (FAK) and c-Src in less than 0.5 s to steeply strengthen α5β1- and αV-class integrin-mediated adhesion. When the mechanical load exceeds a certain threshold, fibroblasts decrease adhesion and initiate the second phase, which is characterized by less steep adhesion strengthening. This unique, biphasic cellular adhesion response is mediated by α5β1 integrins, which form catch bonds with FN and signal to FN-binding integrins to reinforce cell adhesion much before visible adhesion clusters are formed.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/36993
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