title: Substrate stress relaxation regulates cell spreading.
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.
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA [3] Department of Mechanical Engineering, Stanford University, Stanford, California 94305, USA.
authors.forename: Ovijit
authors.initials: O
authors.lastname: Chaudhuri
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Luo
authors.initials: L
authors.lastname: Gu
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Max
authors.initials: M
authors.lastname: Darnell
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA [3] Department of Orthopedic Surgery, Research Institute MOVE, VU University Medical Center, Amsterdam, De Boelelaan 1117, 1081 HV, The Netherlands.
authors.forename: Darinka
authors.initials: D
authors.lastname: Klumpers
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: Sidi A
authors.initials: SA
authors.lastname: Bencherif
authors.affiliation: Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: James C
authors.initials: JC
authors.lastname: Weaver
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Gladstone Institute of Cardiovascular Disease, San Francisco, California 94158, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Huebsch
authors.affiliation: 1] School of Engineering and Applied Sciences, Harvard University, Cambridge, Massachusetts 02138, USA [2] Wyss Institute for Biologically Inspired Engineering, Harvard University, Cambridge, Massachusetts 02138, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Mooney
mesh_terms: D016475:3T3 Cells; D000464:Alginates; D000818:Animals; D002448:Cell Adhesion; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D048430:Cell Shape; D005109:Extracellular Matrix / Q000502:physiology*; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D020100:Hydrogels; D040542:Mechanotransduction, Cellular; D051379:Mice; D008954:Models, Biological; D013314:Stress, Mechanical; D055682:Viscoelastic Substances
chemical_list: D000464:Alginates; D006603:Hexuronic Acids; D020100:Hydrogels; D055682:Viscoelastic Substances; D020723:Glucuronic Acid