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Viscoplasticity Enables Mechanical Remodeling of Matrix by Cells

机译:粘塑性可实现细胞对基质的机械重塑

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摘要

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.
机译:活组织主要由细胞和细胞外基质(ECM)组成。已经发现ECM的机械性质在调节细胞行为如迁移,增殖和分化中起关键作用。尽管迄今为止,大多数研究都集中于阐明基质弹性对细胞行为的影响,但最近的研究表明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,我们严格表征了细胞培养常用材料的可塑性。这种可塑性的表征揭示了在胶原凝胶,重构的基底膜基质,琼脂糖凝胶,藻酸盐凝胶和纤维蛋白凝胶中随时间变化的可塑性或粘塑性,但在聚丙烯酰胺凝胶中却没有。粘塑性与包含弱键的凝胶有关,共价交联减少了胶原蛋白和藻酸盐凝胶中的粘塑性。有趣的是,在胶原蛋白凝胶中发现可塑性程度是非线性的,或者取决于应力或应变的大小,而在其他粘塑性材料中却没有。使用粘塑性模型来描述粘塑性材料中的可塑性。基质粘塑性与细胞-基质相互作用的相关性是通过定量评估细胞对胶原蛋白凝胶的塑性重塑而建立的。发现胶原凝胶的塑性重塑依赖于细胞力,其通过基于整联蛋白的粘附介导,并且甚至在抑制基质的蛋白水解降解的情况下也发生。总之,这些结果表明,基质粘塑性促进了细胞力对基质的塑性重塑。

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