Epithelial Cell-like Elasticity Modulates E-cadherin Adhesion Organization

Abstract

E-cadherin adhesions are essential for cell-to-cell cohesion and mechanical coupling between epithelial cells and reside in a micro-environment that comprises the adjoining epithelial cells. While E-cadherin has been shown to be a mechanosensor, it is unknown if E-cadherin adhesions can differentially sense stiffness within the range of that of epithelial cells. A survey of literature shows that epithelial cells' Young's moduli of elasticity lie predominantly in the sub kPa to few kPa range, with cancer cells often being softer than non-cancerous ones. Here, we devised oriented E-cadherin-coated soft silicone substrates with sub kPa or few kPa elasticity, but with similar viscous moduli, and found that E-cadherin adhesions differentially organize depending on the magnitude of epithelial cell-like elasticity. Linearly shaped E-cadherin adhesions associated with radially oriented actin, but not irregularly shaped E-cadherin adhesions associated with circumferential actin foci, were much more numerous on 2.4 kPa E-cadherin substrates compared to 0.3 kPa E-cadherin substrates. However, the total amount of E-cadherin in both types of adhesions taken together was similar on the 0.3 kPa and 2.4 kPa E-cadherin substrates, across many cells. Furthermore, while the average extent of nuclear recruitment of the mechanoresponsive transcription factor YAP on the 0.3 kPa E-cadherin substrate was undiminished relative to that on the 2.4 kPa substrate, a fraction of cells on the softer substrate displayed relatively high levels of YAP nuclear recruitment. Our results show that E-cadherin adhesions can be regulated by epithelial cell-like elasticity and have significant implications for disease states like carcinomas characterized by altered epithelial cell elasticity.