Substrate Rigidity Regulates the Formation and Maintenance of Tissues

¹ UMass Medical School
² Worcester Polytechnic Institute
³ U Mass Med. School

^* To whom correspondence should be addressed. E-mail: yuli.wang{at}umassmed.edu.

Submitted on July 7, 2005
Revised on July 28, 2005
Accepted on 2 December 2005

	Abstract

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 emigrate 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, while 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.

Key Words: cell adhesion, cell migration, mechanosensing, myosin, small GTPases

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