Physical traits of supercompetitors in cell competition.

Abstract

Cell competition is a fitness control mechanism in tissues, where less fit cells are eliminated to maintain tissue homeostasis. Two primary mechanisms of cell competition have been identified: contact-dependent apoptosis and mechanical stress-induced competition. While both operate in tissues, their combined impact on population dynamics is unclear. Here, we present a cell-based computational model that integrates cellular mechanics with proliferation, contact-induced apoptosis and mechanically triggered apoptosis to investigate competition between two distinct cell types. Using this framework, we systematically examine how differences in physical traits-such as stiffness, adhesion and crowding sensitivity-govern competitive outcomes. Our results show that apoptosis rates alone are insufficient to predict cell fate; differences in proliferation and contact inhibition play equally important, context-dependent roles. Notably, we find that increased cell stiffness can confer a fitness advantage, enabling stiffer cells to outcompete softer neighbours. However, cells with reduced stiffness can become 'soft' supercompetitors if they exhibit faster growth and lower sensitivity to crowding. We also demonstrate that colony size critically influences competition: a minimum size is required for mutant expansion, below which elimination becomes stochastic. This stochastic clearance is driven by a protrusive instability in the interface between two cells that promotes invasion of the supercompetitors.