The determining role of cell adhesions for force transmission, mechanical activity and stiffness sensing in cells and tissues

The role of tissue stiffness in controlling cell behaviours ranging from proliferation to signalling and activation is by now well accepted. A key focus of experimental studies into mechanotransduction are focal adhesions, localised patches of strong adhesion, where cell signalling has been established to occur. However, these adhesion sites themselves alter the mechanical equilibrium of the system determining the force balance and work done. To explore this I have developed an active matter continuum description of cellular contractility and will discuss recent results on the specific role of spatial positioning of adhesions in mechanotransduction. I show using energy arguments why the experimentally observed arrangements of focal adhesions develop and the implications this has for stiffness sensing and cellular contractility control. I will also show how adhesions play distinct roles in single cells and tissue layers respectively drawing on recent experimental work with Dr JR Davis (Manchester University) and Dr Nic Tapon (Crick Institute) with applications to epithelial layers and organoids.