Department of Neurology, University of Vermont, Burlington, Vermont 05405, USA.
J Cell Physiol. 2011 May;226(5):1166-75. doi: 10.1002/jcp.22442.
The visco-elastic behavior of connective tissue is generally attributed to the material properties of the extracellular matrix rather than cellular activity. We have previously shown that fibroblasts within areolar connective tissue exhibit dynamic cytoskeletal remodeling within minutes in response to tissue stretch ex vivo and in vivo. Here, we tested the hypothesis that fibroblasts, through this cytoskeletal remodeling, actively contribute to the visco-elastic behavior of the whole tissue. We measured significantly increased tissue tension when cellular function was broadly inhibited by sodium azide and when cytoskeletal dynamics were compromised by disrupting microtubules (with colchicine) or actomyosin contractility (via Rho kinase inhibition). These treatments led to a decrease in cell body cross-sectional area and cell field perimeter (obtained by joining the end of all of a fibroblast's processes). Suppressing lamellipodia formation by inhibiting Rac-1 decreased cell body cross-sectional area but did not affect cell field perimeter or tissue tension. Thus, by changing shape, fibroblasts can dynamically modulate the visco-elastic behavior of areolar connective tissue through Rho-dependent cytoskeletal mechanisms. These results have broad implications for our understanding of the dynamic interplay of forces between fibroblasts and their surrounding matrix, as well as for the neural, vascular, and immune cell populations residing within connective tissue.
结缔组织的黏弹性行为通常归因于细胞外基质的材料特性，而不是细胞活动。我们之前已经表明，在体腔结缔组织中的成纤维细胞在几分钟内就会对组织拉伸做出动态的细胞骨架重塑，无论是在体外还是体内。在这里，我们检验了这样一个假设，即成纤维细胞通过这种细胞骨架重塑，积极贡献于整个组织的黏弹性行为。当通过抑制叠氮化钠来广泛抑制细胞功能，或者通过破坏微管（用秋水仙碱）或肌动球蛋白收缩性（通过 Rho 激酶抑制）来破坏细胞骨架动力学时，我们测量到组织张力显著增加。这些处理导致细胞体横截面积和细胞场周长减小（通过连接成纤维细胞所有突起的末端获得）。通过抑制 Rac-1 抑制片状伪足形成会减小细胞体横截面积，但不会影响细胞场周长或组织张力。因此，通过改变形状，成纤维细胞可以通过 Rho 依赖性细胞骨架机制动态调节体腔结缔组织的黏弹性行为。这些结果对我们理解成纤维细胞与其周围基质之间的力的动态相互作用具有广泛的意义，也对神经、血管和免疫细胞在结缔组织中的分布具有广泛的意义。
