Abstract

The role of tissue stiffness in controlling cell behaviour is well established. This has been shown across cell types and includes behaviours such as cell differentiation and even drug susceptibility, with clear implications for health and disease. In experimental investigation of mechanosensing, bioengineered gels with defined mechanical properties are used to mimic varying tissue microenvironments. I here present an active matter model for cell contractility and mechanics on controlled stiffness substrates. The model incorporates the observed sub-cellular spatial variations in mechanical activity and adhesion. I show that the stiffness experienced by the cell is not only determined by the actual gel stiffness but rather incorporates the interplay between contractility, cell adhesion patterning and mechanical response. Significantly, I show that focal adhesion growth and elongation is only energetically favourable on stiff substrates, with soft substrates selecting against this behaviour, as is experimentally observed. I will also discuss how this framework scales up in whole tissues looking at recent experimental work by collaborators working with epithelial sheets on patterned substrates.