Analysis of directional cell migration on defined FN gradients: Role of intracellular signaling molecules
Analysis of directional cell migration on defined FN gradients: Role of intracellular signaling molecules
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DOI：
10.1016/j.yexcr.2007.06.005
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发表时间：
2007-11-01
影响因子：
3.7
通讯作者：
Guan, Jun-Lin
中科院分区：
文献类型：
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作者：
Rhoads, Daniel S.;Guan, Jun-Lin
细胞在细胞外基质（ECM）上的定向迁移在胚胎发育和成体生物体中起着重要作用。为了研究定向细胞迁移的调控机制和信号通路，我们使用微流控系统创建了定义的纤连蛋白（FN）梯度。我们发现，成纤维细胞对梯度上更高的FN浓度表现出趋触性。此外，FN梯度方向的净移动与梯度斜率的增加相关，尽管总体迁移率不相关。与之前在均匀涂层表面上的观察结果一致，局部较高的FN浓度由于扩散增加而导致迁移率降低。转染N-WASP或活化Cdc 42，但不FAK或Grb 7，细胞显示出增加的定向迁移。然而，转染FAK，而不是其他信号分子，导致定向细胞迁移的持久性增加，这取决于梯度的斜率以及FAK与PI 3 K的相互作用。总之，这些研究揭示了一些新的特性，定向细胞迁移的定义FN梯度，并建议FAK信号和N-WASP和Cdc 42的差异调节的持久性和速率的定向细胞迁移的作用。(C)2007爱思唯尔公司All rights reserved.
Directional cell migration on extracellular matrix (ECM) plays important roles in embryonic development and adult organisms. To study the mechanisms and signaling pathways involved in the regulation of directional cell migration, we created defined fibronectin (FN) gradients by using microfluidic systems. We found that fibroblasts exhibited haptotaxis towards higher FN concentration on the gradient. Furthermore, the net movements in the direction of FN gradients correlated with the increase in the slope of the gradient although the overall rate of migration was not correlated. Consistent with previous observations on the uniformly coated surface, local higher FN concentration led to reduced migration rate due to increased spreading. Upon transfection of N-WASP or activated Cdc42, but not FAK or Grb7, the cells showed increased directional migration. However, transfection of FAK, but not the other signaling molecules, led to an increase in the persistence of directional cell migration, which is dependent on the slope of the gradient as well as FAK interaction with PI3K. Together, these studies reveal some novel properties of directional cell migration on defined FN gradient and suggested a role for FAK signaling and N-WASP and Cdc42 in the differential regulation of the persistence and rate of directional cell migration. (C) 2007 Elsevier Inc. All rights reserved.