The force loading rate drives cell mechanosensing through both reinforcement and cytoskeletal softening

Ion Andreu, Bryan Falcones, Sebastian Hurst, Nimesh Chahare, Xarxa Quiroga, Anabel-Lise Roux, Zanetta Kechagia, Amy E. M. Beedle, Alberto Elosegui-Artola, Xavier Trepat, Ramon Farré, Timo Betz, Isaac Almendros () and Pere Roca-Cusachs ()
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Ion Andreu: the Barcelona Institute of Technology (BIST)
Bryan Falcones: Universitat de Barcelona
Sebastian Hurst: University of Münster
Nimesh Chahare: the Barcelona Institute of Technology (BIST)
Xarxa Quiroga: the Barcelona Institute of Technology (BIST)
Anabel-Lise Roux: the Barcelona Institute of Technology (BIST)
Zanetta Kechagia: the Barcelona Institute of Technology (BIST)
Amy E. M. Beedle: the Barcelona Institute of Technology (BIST)
Alberto Elosegui-Artola: the Barcelona Institute of Technology (BIST)
Xavier Trepat: the Barcelona Institute of Technology (BIST)
Ramon Farré: Universitat de Barcelona
Timo Betz: University of Münster
Isaac Almendros: Universitat de Barcelona
Pere Roca-Cusachs: the Barcelona Institute of Technology (BIST)

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract Cell response to force regulates essential processes in health and disease. However, the fundamental mechanical variables that cells sense and respond to remain unclear. Here we show that the rate of force application (loading rate) drives mechanosensing, as predicted by a molecular clutch model. By applying dynamic force regimes to cells through substrate stretching, optical tweezers, and atomic force microscopy, we find that increasing loading rates trigger talin-dependent mechanosensing, leading to adhesion growth and reinforcement, and YAP nuclear localization. However, above a given threshold the actin cytoskeleton softens, decreasing loading rates and preventing reinforcement. By stretching rat lungs in vivo, we show that a similar phenomenon may occur. Our results show that cell sensing of external forces and of passive mechanical parameters (like tissue stiffness) can be understood through the same mechanisms, driven by the properties under force of the mechanosensing molecules involved.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24383-3

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DOI: 10.1038/s41467-021-24383-3

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