Control of integrin-mediated mechanorresponse by force loading rates

2018 edition

V├şctor Gonz├ílez-Tarrag├│

Fundamental processes like proliferation, development, and differentiation are affected by tissue rigidity. Cells sense and respond to this rigidity by binding to extracellular matrix (ECM) proteins and applying force through focal adhesions. These adhesions are formed by a complex of proteins, the main one being integrins. Different binding partners modify the response of integrins, thus tuning the adhesion mechanism. This mechanism has been shown to be dependent on substrate rigidity, cell contractility, integrin density, and integrin ligand density. However, the general mechanism underlying these properties is still unknown. Our hypothesis is that changes in the above parameters are just different ways to change integrin loading rates of forces. In this study we used a stretch system to change integrin loading rates independently of any other factor. We found optimum growth of focal adhesions in a range of loading rates in vitro. This was concomitant with an increase in transcription factor YAP1 translocation to the nucleous. This shows that the underlying mechanism of mechanosensing and mechanotransduction is integrin loading rate.