Using Physical Models of Epithelial Sheets to Study Collective Behaviors of Cells

Experiments on epithelial cell sheets reveal many unexplained collective cell behaviors, and simulations offer a promising strategy for understanding how these behaviors arise from cellular level processes. “Active vertex models” are particularly useful because they combine mechanical and migratory properties of cell sheets in a simple framework; we extended these models to include other biological processes. For example, it is not obvious from experiments what causes epithelial tissue to “stick” to a biomimetic boundary coated with E-cadherin; the constituent cells may have maximized their adhesion, lost their migratory drive, or been physically “pinned” to the boundary. Our extended models offer clues for determining what biological processes underlie this behavior. In another experiment, sheets of epithelial cells that are controlled by an external electric field are shown to reverse course via groups of several cells performing independent, coordinated U-turns upon the reversal of the field. We show that this unexpected tissue behavior also emerges in simulated cell sheets by introducing a few simple cell-level rules. In general, this is a powerful approach for making sense of seemingly unexpected experimental results on cell collectives and other multicomponent systems.