This Article Full Text Full Text (PDF) Supplemental All Versions of this Article: biophysj.105.070144v1 90/6/2213    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Guo, W.-h. Articles by Wang, Y.-l. Search for Related Content PubMed PubMed Citation Articles by Guo, W.-h. Articles by Wang, Y.-l.

Substrate Rigidity Regulates the Formation and Maintenance of Tissues

Wei-hui Guo ^*, Margo T. Frey ^* , Nancy A. Burnham  and Yu-li Wang ^*

^* Department of Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605; Department of Biomedical Engineering, and Department of Physics, Worcester Polytechnic Institute, Worcester, Massachusetts 01609

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

The ability of cells to form tissues represents one of the most fundamental issues in biology. However, it is unclear what triggers cells to adhere to one another in tissues and to migrate once a piece of tissue is planted on culture surfaces. Using substrates of identical chemical composition but different flexibility, we show that this process is controlled by substrate rigidity: on stiff substrates, cells migrate away from one another and spread on surfaces, whereas on soft substrates they merge to form tissue-like structures. Similar behavior was observed not only with fibroblastic and epithelial cell lines but also explants from neonatal rat hearts. Cell compaction on soft substrates involves a combination of weakened adhesions to the substrate and myosin II-dependent contractile forces that drive cells toward one another. Our results suggest that tissue formation and maintenance is regulated by differential mechanical signals between cell-cell and cell-substrate interactions, which in turn elicit differential contractile forces and adhesions to determine the preferred direction of cell migration and association.

This article has been cited by other articles:

				A. Szabo, E. Mehes, E. Kosa, and A. Czirok Multicellular Sprouting In Vitro Biophys. J., September 15, 2008; 95(6): 2702 - 2710. [Abstract] [Full Text] [PDF]

				A. Rabodzey, P. Alcaide, F. W. Luscinskas, and B. Ladoux Mechanical Forces Induced by the Transendothelial Migration of Human Neutrophils Biophys. J., August 1, 2008; 95(3): 1428 - 1438. [Abstract] [Full Text] [PDF]

				W.-T. Chiu, M.-J. Tang, H.-C. Jao, and M.-R. Shen Soft Substrate Up-regulates the Interaction of STIM1 with Store-operated Ca2+ Channels That Lead to Normal Epithelial Cell Apoptosis Mol. Biol. Cell, May 1, 2008; 19(5): 2220 - 2230. [Abstract] [Full Text] [PDF]

				A. Veksler and N. S. Gov Phase Transitions of the Coupled Membrane-Cytoskeleton Modify Cellular Shape Biophys. J., December 1, 2007; 93(11): 3798 - 3810. [Abstract] [Full Text] [PDF]

				A. Saez, M. Ghibaudo, A. Buguin, P. Silberzan, and B. Ladoux Rigidity-driven growth and migration of epithelial cells on microstructured anisotropic substrates PNAS, May 15, 2007; 104(20): 8281 - 8286. [Abstract] [Full Text] [PDF]

				M. T. Frey, I. Y. Tsai, T. P. Russell, S. K. Hanks, and Y.-l. Wang Cellular Responses to Substrate Topography: Role of Myosin II and Focal Adhesion Kinase Biophys. J., May 15, 2006; 90(10): 3774 - 3782. [Abstract] [Full Text] [PDF]