Chaudhuri, OvijitGu, LuoDarnell, MaxKlumpers, DarinkaBencherif, SidiWeaver, JamesHuebsch, NathanielMooney, David2016-09-062015Chaudhuri, Ovijit, Luo Gu, Max Darnell, Darinka Klumpers, Sidi A. Bencherif, James C. Weaver, Nathaniel Huebsch, and David J. Mooney. 2015. “Substrate Stress Relaxation Regulates Cell Spreading.” Nat Comms 6 (February 19): 6365. doi:10.1038/ncomms7365.2041-1723http://nrs.harvard.edu/urn-3:HUL.InstRepos:28265472Studies 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.en-USJournal Article2016-09-0610.1038/ncomms7365