Extracellular matrix type modulates cell migration on mechanical gradients.

Extracellular matrix type modulates cell migration on mechanical gradients.
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DOI:
10.1016/j.yexcr.2017.08.018
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发表时间:
2017-10-15
影响因子:
3.7
通讯作者:
Wong JY
Wong JY
中科院分区:
医学3区
文献类型:
--
作者:
Hartman CD;Isenberg BC;Chua SG;Wong JY

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已知细胞外基质组成和硬度是细胞行为的关键决定因素,调节包括分化、牵引力产生和迁移在内的过程。最近的研究表明,细胞外基质成分可以调节细胞如何迁移,以响应环境刚性的梯度,改变细胞接受趋化的能力。这些观察仅限于单一种类的细胞外基质,通常细胞暴露在含有复杂的细胞外基质蛋白混合物的环境中。在这里,我们研究了NIH3T3成纤维细胞在包被一种或多种细胞外基质蛋白的机械梯度上的迁移。我们的结果表明,NIH3T3成纤维细胞在纤维连接蛋白包被的机械梯度上表现出趋向性,而在那些包被层粘连蛋白的成纤维细胞上不表现出趋向性,这表明细胞外基质类型可以作为细胞对机械梯度的反应的调节器。有趣的是,还观察到NIH3T3成纤维细胞在涂有纤维连接蛋白和层粘连蛋白混合物的梯度上随机迁移,这表明在多种细胞外基质信号存在的情况下,细胞对机械梯度的反应可能存在复杂的相互作用。这些发现表明,可用黏附配体的特定组成是细胞对机械梯度的迁移反应的关键决定因素。
Extracellular matrix composition and stiffness are known to be critical determinants of cell behavior, modulating processes including differentiation, traction generation, and migration. Recent studies have demonstrated that the ECM composition can modulate how cells migrate in response to gradients in environmental stiffness, altering a cell’s ability to undergo durotaxis. These observations were limited to single varieties of extracellular matrix, and typically cells are exposed to environments containing complex mixtures of extracellular matrix proteins. Here, we investigate migration of NIH 3T3 fibroblasts on mechanical gradients coated with one or more type of extracellular matrix protein. Our results show that NIH 3T3 fibroblasts exhibit durotaxis on fibronectin-coated mechanical gradients but not on those coated with laminin, demonstrating that extracellular matrix type can act as a regulator of cell response to mechanical gradients. Interestingly, NIH 3T3 fibroblasts were also observed to migrate randomly on gradients coated with a mixture of both fibronectin and laminin, suggesting that there may be a complex interplay in the cellular response to mechanical gradients in the presence of multiple extracellular matrix signals. These findings indicate that specific composition of available adhesion ligands is a critical determinant of a cell’s migratory response to mechanical gradients.
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