Vascular smooth muscle cell durotaxis depends on extracellular matrix composition
Vascular smooth muscle cell durotaxis depends on extracellular matrix composition
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DOI：
10.1073/pnas.1611324113
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发表时间：
2016-10-04
影响因子：
11.1
通讯作者：
Wong, Joyce Y.
中科院分区：
文献类型：
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作者：
Hartman, Christopher D.;Isenberg, Brett C.;Wong, Joyce Y.
机械顺应性已被证明是细胞行为的关键决定因素，指导诸如扩散、迁移和分化的过程。已经在多种细胞类型中观察到了趋硬性，即从基质的较软区域向较硬区域的定向迁移。最近的硬度映射实验表明，疾病中组织硬度的局部变化通常伴随着体内ECM组成的改变。然而，ECM成分在硬脊膜扩张中的重要性尚未得到探讨。为了解决这个问题，我们已经开发并表征了一种聚丙烯酰胺水凝胶培养平台，其具有高度可调的机械刚度梯度。这一特征，连同控制ECM组成的能力，使我们能够分离机械和生物信号对细胞迁移行为的影响。使用这个系统，我们已经跟踪血管平滑肌细胞迁移在体外和定量分析细胞迁移的ECM组合物的功能的差异。我们的研究结果表明，血管平滑肌细胞进行durotaxis上的机械梯度与纤维连接蛋白，但不与层粘连蛋白。这些发现表明，粘附配体的组成是细胞对机械梯度的迁移反应的关键决定因素。
Mechanical compliance has been demonstrated to be a key determinant of cell behavior, directing processes such as spreading, migration, and differentiation. Durotaxis, directional migration from softer to more stiff regions of a substrate, has been observed for a variety of cell types. Recent stiffness mapping experiments have shown that local changes in tissue stiffness in disease are often accompanied by an altered ECM composition in vivo. However, the importance of ECM composition in durotaxis has not yet been explored. To address this question, we have developed and characterized a polyacrylamide hydrogel culture platform featuring highly tunable gradients in mechanical stiffness. This feature, together with the ability to control ECM composition, allows us to isolate the effects of mechanical and biological signals on cell migratory behavior. Using this system, we have tracked vascular smooth muscle cell migration in vitro and quantitatively analyzed differences in cell migration as a function of ECM composition. Our results show that vascular smooth muscle cells undergo durotaxis on mechanical gradients coated with fibronectin but not on those coated with laminin. These findings indicate that the composition of the adhesion ligand is a critical determinant of a cell's migratory response to mechanical gradients.