期刊
EXPERIMENTAL CELL RESEARCH
卷 313, 期 18, 页码 3859-3867出版社
ELSEVIER INC
DOI: 10.1016/j.yexcr.2007.06.005
关键词
cell migration; extracellular matrix gradients; cell signaling; focal adhesion kinase
资金
- NIGMS NIH HHS [R01 GM048050-15, R01 GM048050, GM48050] Funding Source: Medline
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.
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