Sheet migration by wounded monolayers as an emergent property of single-cell dynamics

Abstract

Multi-cell migration is important for tissue development and repair. An experimentally accessible example of multi-cell migration is provided by the classic scratch-wound assay. In this assay, a confluent monolayer is `injured' by forcibly removing a strip of cells, and the remaining monolayer `heals' through some combination of cell migration, spreading and proliferation. The scratch wound has been used for decades as a model of wound healing and an assay of cell migration, however the mechanisms that underlie the coherent expansion of cells in the surviving monolayer are still debated. Here we develop an agent-based computational model that predicts the most robust characteristics of healing in scratch wounds. The cells in our model are simple mechanical agents that respond to cell contact by redirecting migration and slowing division. We imbued model cells with crawling and growth dynamics and measured for individual L1 fibroblasts and found that simulated recovery occurs in a steady, sheet-like and division-independent fashion to mimic healing by L1s. The lack of cohesion and biochemical cell-cell communication in the model suggests that these factors are not strictly necessary for cells to migrate as a group. Instead, our analysis suggests that steady sheet migration can be explained by cell spreading in the monolayer.