Substrate stress relaxation regulates cell spreading

TLDR

Cellular mechanotransduction studies show that cells sense ECM elasticity by resisting traction forces, but most use purely elastic substrates while physiological ECM is viscoelastic and relaxes stress, which may alter cell responses. The study aims to determine how ECM stress relaxation affects cell behavior. The authors employ computational modeling and cellular experiments to evaluate the impact of ECM stress relaxation. Both modeling and experiments reveal that soft viscoelastic substrates promote greater cell spreading—comparable to stiffer elastic substrates—contradicting the prevailing view of ECM sensing.

Abstract

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.