Viscoelastic properties of microgel thin films control fibroblast modes of migration and pro-fibrotic responses
Viscoelastic properties of microgel thin films control fibroblast modes of migration and pro-fibrotic responses
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DOI：
10.1016/j.biomaterials.2018.09.012
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发表时间：
2018-12-01
期刊：
影响因子：
14
通讯作者：
Brown, Ashley C.
中科院分区：
文献类型：
--
作者：
Chester, Daniel;Kathard, Rahul;Brown, Ashley C.
细胞的行为受到其微环境的生物物理性质的影响，而底物的线弹性性质强烈地影响着细胞的黏附、迁移和分化反应。由于大多数生物组织表现出非线性弹性特性，人们对了解材料和组织的粘性成分如何影响细胞命运越来越感兴趣。在这里，我们描述了使用具有可控非线性弹性的微凝胶薄膜来研究材料损失切线在细胞黏附、迁移和肌成纤维细胞分化中的作用，这在纤维化反应中具有重要意义。成纤维细胞的迁移方式由膜损失切线决定；高损失切线诱导岩石介导的阿米巴迁移，而低损失切线诱导RAC介导的间充质细胞迁移。低损耗的切线膜也与较高水平的肌成纤维细胞分化有关。这些发现对纤维化有意义，并表明损伤后组织粘弹性的轻微变化可能有助于早期启动与纤维化相关的反应。
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.