Experimental and computational modelling of collective cell migration in peripheral nerve repair

Abstract

A number of biological processes, such as embryonic development, cancer invasion and wound repair, rely on collective cell migration, a process of cells migrate together in sheets, strands or clusters. Peripheral nerves have a remarkable ability to regenerate and re-establish function after injury. Our lab has previously shown that this process depends on the collective migration of Schwann cell cords into the wound, which guide regrowing axons across the injury site to promote re-innervation. Cell-cell contact dependent signalling between Schwann cells and wound fibroblasts plays a critical role in this process by promoting cord formation and directional migration through Eph/ephrin-dependent cell sorting. However, how the interplay of homotypic and heterotypic cell-cell interactions regulates the coherent collective migration of Schwann cells or which molecular are effectors involved is not fully understood. We combine cell and molecular biology experiments with computational simulations to develop a novel computational model of peripheral nerve repair which simulates the interactions between Schwann cells and fibroblasts at the wound site. First, using methods from statistical physics we analyse experimental \emph{in vitro} data to parametrize our model. Then, we use the model to explore the theoretical requirements for an emerging coordination (i.e. formation of collectively migrating Schwann cell cords) in the system in order to better understand the mechanisms by which peripheral nerve repair occurs.