Epithelial Monolayers Coalesce on a Viscoelastic Substrate through Redistribution of Vinculin.

The mechanical properties of the microenvironment play a large role in influencing cellular behavior. In particular, the tradeoff between substrate viscosity and elasticity on collective cell migration by adherent cells is highly physiologically relevant, but remains poorly understood. To investigate the specific effects of viscous substrates, we plated epithelial monolayers onto polydimethylsiloxane substrata with a range of viscosities and elasticities. We found that on viscoelastic substrates the monolayers underwent rapid and coordinated movement to generate cell-free areas. To understand the molecular mechanism of this coordinated movement, we imaged various structural and signaling proteins at cell-cell and cell-matrix junctions. Through quantitative image analysis of monolayer disruption and subcellular protein redistribution, we show that the mechanosensor protein, vinculin, is necessary and sufficient for this viscous response, during which it is lost from focal adhesions and recruited by the cadherin complex to intercellular junctions. In addition, the viscous response is dependent upon and enhanced by actomyosin contractility. Our results implicate vinculin translocation in a molecular switching mechanism that senses substrate viscoelasticity and associates with actomyosin contractility.