Chaudhuri Ovijit, Gu Luo, Darnell Max, Klumpers Darinka, Bencherif Sidi A, Weaver James C, Huebsch Nathaniel, Mooney David J
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.
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.
Nat Commun. 2015 Feb 19;6:6364. doi: 10.1038/ncomms7365.
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.
细胞机械转导的研究集中于这样一种观点,即细胞通过测量它们施加于细胞外基质(ECM)上的牵引力的阻力来感知ECM弹性。然而,这些研究通常使用纯弹性材料作为底物,而生理ECM是粘弹性的,并表现出应力松弛,因此细胞施加的细胞牵引力会重塑ECM。在这里,我们通过计算建模和细胞实验研究ECM应力松弛对细胞行为的影响。令人惊讶的是,我们的计算模型和实验均发现,在表现出应力松弛的软底物上培养的细胞的铺展大于在相同模量的弹性底物上培养的细胞,但与在更硬的弹性底物上铺展的细胞相似。这些发现挑战了目前关于细胞如何感知和响应ECM的观点。