Cellular Responses to 3D Substrate Topography: Role of Myosin II and Focal Adhesion Kinase
Margo T. Frey 1, Irene Y. Tsai 2, Thomas P. Russell 2, Steven K. Hanks 3 and Yu Li Wang 4*
1 University of Massachusetts Medical School
2 University of Massachusetts, Amherst
3 The Vanderbilt-Ingram Cancer Center
4 U Mass Med. School
* To whom correspondence should be addressed. E-mail: yuli.wang{at}umassmed.edu.
Submitted on September 15, 2005
Revised on December 8, 2005
Accepted on 6 February 2006
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Abstract |
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Although 2D cultures have been used extensively in cell biological research, most cells in vivo exist in a 3D environment with complex topographical features, which may account for at least part of the striking differences between cells grown in vivo and in vitro. To investigate how substrate topography affects cell shape and movement, we plated fibroblasts on chemically identical polystyrene substrates with either flat surfaces or micron-sized pillars. Compared to cells on flat surfaces, 3T3 cells on pillar substrates showed a more branched shape, an increased linear speed, and a decreased directional stability. These responses may be attributed to stabilization of cell adhesion on pillars coupled to myosin II-dependent contractions toward pillars. Moreover, using FAK-/- fibroblasts we showed that FAK is essential for the responses to substrate topography. We propose that increased surface contact provided by topographic features guides cell migration by regulating the strength of local adhesions and contractions, through a FAK-and myosin II-dependent mechanism.
Key Words:
FAK, cell migration, contact guidance, mechanosensing, myosin, topography
