A novel mode of cell detachment from fibrillar fibronectin matrix under shear
A novel mode of cell detachment from fibrillar fibronectin matrix under shear
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DOI：
10.1242/jcs.040824
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发表时间：
2009-05-15
影响因子：
4
通讯作者：
Schwarzbauer, Jean E.
中科院分区：
文献类型：
--
作者：
Engler, Adam J.;Chan, May;Schwarzbauer, Jean E.
组织内的细胞被纤维细胞外基质（ECM）包围，通过整合素受体支持细胞粘附。细胞与纤维基质相互作用的强度以及力对这些相互作用的影响尚未被量化。为此，我们使用旋转圆盘装置对附着在细胞源性纤维连接蛋白（FN）基质上的HT1080纤维肉瘤细胞施加径向增加的剪切。分离50% HT1080细胞所需的剪切力在FN涂层的刚性玻璃基板上是纤原FN基质上的8倍。FN基质的共价交联使其刚度增加了十倍，并使这些细胞的剪切分离力适度增加。在FN包覆的表面上，细胞通过释放α 5 β 1整合素和FN之间的相互作用而分离。相比之下，细胞脱离原纤维基质是通过一种新的原纤维断裂机制发生的，在荧光显微镜下可以看到在基质中留下孔。这些结果表明，细胞从纤维基质中分离所需的力比从玻璃上吸附的FN中分离所需的力小，并且分离是通过破坏原纤维而不是通过释放整合素-基质键来实现的。因此，在理解细胞和组织稳态时，外膜原纤维断裂是另一个需要考虑的分子特征。
Cells within tissues are surrounded by fibrillar extracellular matrix (ECM) that supports cell adhesion via integrin receptors. The strength of cell interactions with fibrillar matrix and the effects of force on these interactions have not been quantified. To this end, we used a spinning disc device to apply radially increasing shear to human HT1080 fibrosarcoma cells attached to a cell-derived fibrillar fibronectin (FN) matrix. The shear required to detach 50% of HT1080 cells was eight times greater on a FN-coated, rigid glass substrate than on fibrillar FN matrix. Covalent crosslinking of the FN matrix increased its stiffness tenfold and produced a modest increase in shear detachment force for these cells. On FN-coated surfaces, cells detach by releasing interactions between alpha 5 beta 1 integrin and FN. By contrast, cell detachment from fibrillar matrix occurred through a novel mechanism of fibril breakage, which left holes in the matrix visible by fluorescence microscopy. These results show that cells require less force to detach from fibrillar matrix than from FN adsorbed on glass and that detachment occurs through breaking fibrils instead of by release of integrin-matrix bonds. Thus, ECM fibril breakage is another molecular feature to consider when understanding cell and tissue homeostasis.