Viscoplasticity Enables Mechanical Remodeling of Matrix by Cells

Viscoplasticity Enables Mechanical Remodeling of Matrix by Cells
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DOI:
10.1016/j.bpj.2016.10.002
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发表时间:
2016-11-15
影响因子:
3.4
通讯作者:
Chaudhuri, Ovijit
Chaudhuri, Ovijit
中科院分区:
生物学3区
文献类型:
--
作者:
Nam, Sungmin;Lee, Joanna;Chaudhuri, Ovijit

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活组织主要由细胞和细胞外基质(ECM)组成。ECM的力学性质在调节细胞迁移、增殖和分化等行为中起着关键作用。尽管迄今为止大多数研究都集中在阐明基质弹性对细胞行为的影响,但最近的研究揭示了基质粘弹性对细胞行为的影响,并报道了细胞对ECM的塑性重塑。在这项研究中,我们严格的特点,可塑性的材料,通常用于细胞培养。可塑性的这种表征显示时间依赖性的可塑性,或粘塑性,在胶原蛋白凝胶,重建基底膜基质,琼脂糖凝胶,藻酸盐凝胶,和纤维蛋白凝胶,但不是在聚丙烯酰胺凝胶。粘塑性与含有弱键的凝胶相关,共价交联降低了胶原蛋白和藻酸盐凝胶的粘塑性。有趣的是,可塑性的程度被发现是非线性的,或依赖于应力或应变的大小,在胶原蛋白凝胶,但不是在其他粘塑性材料。采用粘塑性模型来描述粘塑性材料的塑性。通过定量评估细胞对胶原凝胶的塑性重塑,建立了基质粘塑性与细胞基质相互作用的相关性。胶原蛋白凝胶的塑性重塑被认为是依赖于细胞的力量,介导的整合素为基础的粘附,甚至发生与基质的蛋白水解降解的抑制。总之,这些结果表明,基质的粘塑性有利于塑性重塑的基质细胞的力量。
Living tissues consist largely of cells and extracellular matrices (ECMs). The mechanical properties of ECM have been found to play a key role in regulating cell behaviors such as migration, proliferation, and differentiation. Although most studies to date have focused on elucidating the impact of matrix elasticity on cell behaviors, recent studies have revealed an impact of matrix viscoelasticity on cell behaviors and reported plastic remodeling of ECM by cells. In this study, we rigorously characterized the plasticity in materials commonly used for cell culture. This characterization of plasticity revealed time-dependent plasticity, or viscoplasticity, in collagen gels, reconstituted basement membrane matrix, agarose gels, alginate gels, and fibrin gels, but not in polyacrylamide gels. Viscoplasticity was associated with gels that contained weak bonds, and covalent cross-linking diminished viscoplasticity in collagen and alginate gels. Interestingly, the degree of plasticity was found to be nonlinear, or dependent on the magnitude of stress or strain, in collagen gels, but not in the other viscoplastic materials. Viscoplastic models were employed to describe plasticity in the viscoplastic materials. Relevance of matrix viscoplasticity to cell matrix interactions was established through a quantitative assessment of plastic remodeling of collagen gels by cells. Plastic remodeling of collagen gels was found to be dependent on cellular force, mediated through integrin-based adhesions, and occurred even with inhibition of proteolytic degradation of the matrix. Together, these results reveal that matrix viscoplasticity facilitates plastic remodeling of matrix by cellular forces.