Integrin-dependent actomyosin contraction regulates epithelial cell scattering

Abstract

The scattering of Madin-Darby canine kidney cells in vitro mimics key aspects of epithelial–mesenchymal transitions during development, carcinoma cell invasion, and metastasis. Scattering is induced by hepatocyte growth factor (HGF) and is thought to involve disruption of cadherin-dependent cell–cell junctions. Scattering is enhanced on collagen and fibronectin, as compared with laminin1, suggesting possible cross talk between integrins and cell–cell junctions. We show that HGF does not trigger any detectable decrease in E-cadherin function, but increases integrin-mediated adhesion. Time-lapse imaging suggests that tension on cell–cell junctions may disrupt cell–cell adhesion. Varying the density and type of extracellular matrix proteins shows that scattering correlates with stronger integrin adhesion and increased phosphorylation of the myosin regulatory light chain. To directly test the role of integrin-dependent traction forces, substrate compliance was varied. Rigid substrates that produce high traction forces promoted scattering, in comparison to more compliant substrates. We conclude that integrin-dependent actomyosin traction force mediates the disruption of cell–cell adhesion during epithelial cell scattering.

Scattering of Cell Clusters in Confinement

“…3 d). Thus, the CE adhesions and the CC junctions have an antagonistic relationship, consistent with previous experimental findings of integrincadherin crosstalk (19,30). The reduced stabilization of CEs in softer ECMs caused low protrusion and actomyosin forces, which in turn disabled the dissociation rate of CC junctions.…”

“…Over the years, numerous experimental studies have revealed new phenotypes of mechanosensitive and ECMdependent cell scattering and EMT (1)(2)(3)(4)9,13,19,31,32). However, a clear conceptual framework of how cellular mechanisms of forces and adhesions physically interact with the ECM and enable EMT was missing.…”

“…In multicell clusters, the integrin-cadherin crosstalk (18,19) dictates that greater number of CC junctions (b) slows down CE bond formation. We combine these two influences of cell-ECM and cellcell interactions to describe the rate of formation of CE bonds for each node (a) as follows:…”

“…According to the known integrin-cadherin crosstalk (18,19), the cell-ECM adhesions (greater b a) oppose the formation of CC junctions. Thus, the net rate of change of the number of CC junctions at any node is as follows:…”

Rho GTPases in osteoclasts: Orchestrators of podosome arrangement

“…However, how the mineralized matrix or mineral by itself may affect RhoGTPase activity and then osteoclast function is an open question. An emerging theme is that adhesion strength and substrate stiffness regulate cell migration and adhesion structure organization (de Rooij et al, 2005;Gupton and Waterman-Storer, 2006). In turn, cells adjust their internal stiffness to match that of their substrate (Solon et al, 2007).…”