All our tissues consist of cells set into a complex extracellular matrix of proteins and sugars. The extracellular matrix not only embeds the cells in the tissue, it provides the essential mechanical properties of each tissue: the hardness of bone, the elasticity of skin and the toughness of tendons, for instance. Down at the nanoscopic lengthscale, the extracellular matrix instructs cells how to behave in that tissue. The instructions are delivered by molecules in the extracellular matrix binding to specific proteins on the surface of the tissue’s cells. So, the detailed molecular structure and organization of the extracellular matrix determines the instructions given to cells. But that extracellular matrix structure is subject to constant movement because of the external forces we subject our tissues to. This project investigates how the extracellular matrix molecular structures change as tissues are stretched and even torn, and then linking those structural changes to altered cell behaviour. Understanding how tissue mechanics affects cell behaviour is fundamental to understanding how our tissues work – and how they fail. The extracellular matrix structure changes hugely with injury and in diseases like cancer, and the changed matrix structure drives altered cell behaviours that often lead to poor outcomes, like imperfect tissue repair or progression of cancer. However, knowledge of how the extracellular matrix molecular structure translates to instructions to cells is still a work in progress in science. Understanding what is actually changing in the extracellular matrix structure and how that impacts cell behaviour is the essential starting point to design therapeutic interventions, to improve tissue repair and even to inhibit cancer progression.
