Cell behavior is influenced by the biophysical properties of their microenvironments, and the linear elastic properties of substrates strongly influences adhesion, migration, and differentiation responses. Because most biological tissues exhibit non-linear elastic properties, there is a growing interest in understanding how the viscous component of materials and tissues influences cell fate. Here we describe the use of microgel thin films with controllable non-linear elastic properties for investigating the role of material loss tangent on cell adhesion, migration, and myofibroblastic differentiation, which have implications in fibrotic responses. Fibroblast modes of migration are dictated by film loss tangent; high loss tangent induced ROCK-mediated amoeboid migration while low loss tangent induced Rac-mediated mesenchymal cell migration. Low loss tangent films were also associated with higher levels of myofibroblastic differentiation. These findings have implications in fibrosis and indicate that slight changes in tissue viscoelasticity following injury could contribute to early initiation of fibrotic related responses.

细胞行为受其微环境的生物物理特性影响，并且底物的线性弹性特性强烈影响粘附，迁移和分化反应。由于大多数生物组织都表现出非线性弹性特性，因此人们越来越了解材料和组织的粘性成分如何影响细胞命运。在这里，我们描述了具有可控的非线性弹性特性的微凝胶薄膜的使用，用于研究材料损耗角正切对细胞粘附，迁移和肌纤维母细胞分化的作用，这些作用在纤维化反应中具有重要意义。成纤维细胞的迁移方式取决于薄膜的损耗角正切。高损耗正切引起ROCK介导的类动植物迁移，而低损耗正切引起Rac介导的间充质细胞迁移。低损耗正切膜也与较高水平的肌成纤维细胞分化有关。这些发现与纤维化有关，表明损伤后组织粘弹性的细微变化可能有助于纤维化相关反应的早期启动。