Mechanical regulation of collective cell migration and wound healing

Collective cell migration is essential in several fundamental biological processes: during morphogenesis, cells display highly coordinated shape changes, rearrangements, and movements; during wound healing, cells must coordinate their migration to close gaps in epithelial tissues to maintain tissue integrity and prevent infection. The efficiency of these processes is determined by mechanics. Cells actively produce contractile forces to deform, but display elastic behaviour resisting long scale deformation. Cells must actively adhere to and apply traction forces to the substrate to crawl, but the speed of movement depends on the stiffness of the substrate. The aim of this project is to use computational methods to investigate how the mechanical properties of both the cells and their environments regulates these processes. This theoretical work will be done in close collaboration with experimental groups from Yale University, University of Chicago, and UCL.
One particular area of cell migration that this project will focus on is wound healing. Gaps in the epithelial tissue can be closed through two main mechanisms: a supra-cellular actomyosin cable contracts the wound like a purse-string, or collective cell crawling. The choice of these mechanisms has been observed to depend on the wound size, geometry, and substrate stiffness. Thus, one project aim is to investigate how the efficiency of closure changes when these properties vary, in terms of closure time, and power exerted by the cells. Moreover, the properties of the cells regulate the efficiency of movement; stiff, contractile cells will display more resistance to motion but produce higher forces at the wound edge, while softer cells display more fluid behaviour under forces.
We will also aim to understand collective cell migration and shape changes at a smaller scale. Forces driving shape changes often act at cell-cell junctions. However, cells are not just a simple elastic material, but are active systems and can respond to stress, through relaxation or stiffening. We will develop theoretical equations for mechanosensitive remodelling at cell-cell junctions, by investigating the response using optogenetic tools to induce localised contractions.