Individual and Collective Events in Cell Competition Dynamics using a Cellular Potts Model

Cell competition is a quality control mechanism that results in the elimination of less fit cells from a tissue. Studies in recent years have revealed that cell competition can either be driven by long-range mechanical stresses in the tissue or by short-range cell contact-dependent biochemical signaling. While mechanical competition arises from a difference in homeostatic density leading to a pressure gradient that drives cell elimination, biochemical competition results in an increased rate of apoptosis at the interface between two cell types. How these two mechanisms cooperate or compete to regulate tissue homeostasis remains unknown. Here we develop a Cellular Potts model for cell competition using parameters determined from cultured epithelial cells. Using this model, we determine the biophysical parameters that control the three possible outcomes of competition: elimination of mutant cells, elimination of wild type cells, and the coexistence of mutants with the wild type cells. We further investigate how the interplay between cell division, cell extrusion, and programmed cell death regulates tissue homeostasis and collective population dynamics. We compare these findings with a population-scale mathematical model for cell competition.