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 elimination have been identified in cell competition studies: contact-dependent cell death and mechanical compression-driven apoptosis. While both occur in tissues, their combined impact on population dynamics is unclear. Here we develop a cell-based computational model to study competition between two cell types with differing physical properties. The model integrates cellular mechanics with cell-cycle dynamics, contact-induced apoptosis, and cell extrusion via mechanical stress. Using this model, we explored how differences in physical traits between cell types influence competitive interactions. Our findings show that differences in cell compressibility alone can drive mechanical competition, with stiffer cells outcompeting softer ones in otherwise identical populations. Surprisingly, mutations that reduce cell stiffness, combined with decreased contact inhibition of proliferation, can create a "soft" super-competitive mutant. We demonstrate that changes in apoptosis sensitivity, cell adhesion, and cell size significantly affect growth potential and susceptibility to apoptosis. Furthermore, mutant cell colonies require a critical colony size, dependent on cell compressibility, to overtake the surrounding wild-type tissue. For colonies below the critical size, the elimination process is stochastic, driven by a protrusive finger-like instability in the interface between two cells that promote invasion of the supercompetitors.