Adhesion-mediated force transmission regulates cell competition in epithelia

Organs and tissues consist of a precise arrangement of different cell types, all playing a specific role to fulfil the biological function of the tissue. Small changes in cellular phenotypes or behaviour can lead to developmental defects, tissue malfunctions or the emergence of diseases. Therefore, tissue integrity, health and function are maintained through different quality control mechanisms. One highly conserved mechanism is cell competition, through which cells of reduced fitness are eliminated. Cells can employ various strategies to eliminate each other. Those include the exertion of mechanical forces, but its role in determining the competition outcome remains unclear. Here, we report that heterogeneities in force transmission capabilities mediated by cell-cell adhesion differences lead to cell competition. We show that increased force transmission endows collectives of cells with a fitness advantage, as it provides increased resistance to elimination forces. Elimination forces are generated from large stress fluctuations, emerging at the interfaces of competing cell populations. Besides promoting the removal of unfit cells in a wide range of biological conditions where local cell-cell adhesion heterogeneities are observed, this mechanism might be of general importance for the generation and maintenance of tissue boundaries.