Substrate stress relaxation regulates cell spreading

Studies of cellular mechanotransduction have converged upon the idea that cells sense extracellular matrix (ECM) elasticity by gauging resistance to the traction forces they exert on the ECM. However, these studies typically utilize purely elastic materials as substrates, whereas physiological ECMs are viscoelastic, and exhibit stress relaxation, so that cellular traction forces exerted by cells remodel the ECM. Here we investigate the influence of ECM stress relaxation on cell behaviour through computational modelling and cellular experiments. Surprisingly, both our computational model and experiments find that spreading for cells cultured on soft substrates that exhibit stress relaxation is greater than cells spreading on elastic substrates of the same modulus, but similar to that of cells spreading on stiffer elastic substrates. These findings challenge the current view of how cells sense and respond to the ECM. Studies of cellular mechanotransduction commonly use elastic substrates, whereas biological substrates are viscoelastic, exhibiting stress relaxation. Here, the authors show through computational modelling and experiments that viscoelastic substrates can stimulate cell spreading to a greater extent than purely elastic substrates with the same initial stiffness.