A cellular automaton based on plasma membrane turnover accurately recapitulates cell mechanics during epithelial scattering

Abstract

Epithelial cells can be triggered to actively detach from epithelial tissues and become solitary, migratory and invasive. This process occurs repeatedly in development, where it is termed epithelial-mesenchymal transition (EMT), and can be recapitulated as epithelial scattering in cell culture models. Detachment of cell-cell junctions involves changes in contractile forces, actin cytoskeletal organization, changes in cell-substrate adhesion properties, surface presentation of cell-cell adhesion molecules, and gene expression. That these cellular processes affect each other and share molecular components creates difficulties in generating hypotheses and designing experiments to understand the mechanics of epithelial scattering. Computational modeling is proving a powerful too in such instances. Here we develop a cellular automaton to reveal insights into how cells rupture epithelial cell-cell junctions during scattering. The model is optimized for realistic and stable recapitulation of behavior of single cells, then for realistic simulation of multiple cells forming epithelial colonies. With a workable model of epithelial cell behavior, we then alter model parameters and assess whether we can realistically mimic epithelial scattering. Adjusting model parameters to recapitulate epithelial scattering reveals that induction of cell migration is the major driver of epithelial scattering.