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Departments of Pathology and Surgery, Children’s Hospital, Harvard Medical School;
* Physiology Program, Harvard School of Public Health, Boston, Massachusetts, USA;
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts, USA;
Department of Physics, Boston University, Boston, Massachusetts, USA; and
MRC Laboratory for Molecular Cell Biology and Department of Biochemistry and Molecular Biology, University College London, London, UK
1Correspondence: Departments of Surgery and Pathology, Children’s Hospital-Harvard Medical School, Enders 1007, 300 Longwood Ave., Boston, MA 02115, USA. E-mail: donald.ingber{at}tch.harvard.edu
Directed cell migration is critical for tissue morphogenesis and wound healing, but the mechanism of directional control is poorly understood. Here we show that the direction in which cells extend their leading edge can be controlled by constraining cell shape using micrometer-sized extracellular matrix (ECM) islands. When cultured on square ECM islands in the presence of motility factors, cells preferentially extended lamellipodia, filopodia, and microspikes from their corners. Square cells reoriented their stress fibers and focal adhesions so that tractional forces were concentrated in these corner regions. When cell tension was dissipated, lamellipodia extension ceased. Mechanical interactions between cells and ECM that modulate cytoskeletal tension may therefore play a key role in the control of directional cell motility.—Parker, K. K., Brock, A. L., Brangwynne, C., Mannix, R. J., Wang, N., Ostuni, E., Geisse, N. A., Adams, J. C., Whitesides, G. M., Ingber, D. E. Directional control of lamellipodia extension by constraining cell shape and orienting cell tractional forces.
Key Words: migration • motility • focal adhesion • cell tension • microspike • microcontact printing
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