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Cellular Responses to Substrate Topography: Role of Myosin II and Focal Adhesion Kinase

Margo T. Frey ^* , Irene Y. Tsai , Thomas P. Russell , Steven K. Hanks  and Yu-li Wang ^*

^* Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605; Department of Biomedical Engineering, Worcester Polytechnic Institute, Worcester, Massachusetts 01609; Department of Polymer Science and Engineering, University of Massachusetts, Amherst, Massachusetts 01003; and Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232

Correspondence: Address reprint requests to Yu-li Wang, PhD, University of Massachusetts Medical School, 377 Plantation Ave., Suite 327, Worcester, MA 01605. Tel.: 508-856-8781; Fax: 508-856-8774; E-mail: yuli.wang{at}umassmed.edu.

Although two-dimensional cultures have been used extensively in cell biological research, most cells in vivo exist in a three-dimensional 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 focal adhesion kinase, or 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.