A mathematical framework for the emergence of winners and losers in cell competition

Abstract

Cell competition is a process in multicellular organisms where cells interact with their neighbours to determine a "winner" or "loser" status. The loser cells are eliminated through programmed cell death, leaving only the winner cells to populate the tissue. Cell competition is context-dependent; the same cell type can win or lose depending on the cell type it is competing against. Hence, winner/loser status is an emergent property. A key question in cell competition is: how do cells acquire their winner/loser status? In this paper, we propose a mathematical framework for studying the emergence of winner/loser status based on a set of quantitative criteria that distinguishes competitive from non-competitive outcomes. We apply this framework in a cell-based modelling context, to both highlight the crucial role of active cell death in cell competition and identify the factors that drive cell competition. HighlightsO_LIEmergent winner/loser status tests for competitive outcomes in cell-based models C_LIO_LIDifferences in biomechanical properties alone are not sufficient for cell competition C_LIO_LIWinners have both higher tolerance and higher emission of death signals than losers C_LI