Cell size regulation and growth control in crowded tissues

Regulation of cell size and growth within a crowded tissue is critical to reach and maintain homeostasis. While most studies to date have characterized tissue homeostasis and growth control at the population-level, there are no available models that connect cellular growth dynamics and mechanics to the emergent tissue-level dynamics. Using parameters determined from experiments on cultured epithelial cells, we develop a multi-scale Cellular Potts model that describes the dynamics of a tissue transitioning from a sub-confluent state to a state of arrested growth. The model addresses how tissue crowding influences cell growth, size regulation and division dynamics. Using this model, we quantify how a cell's sensitivity to crowding, deformation, cell-cell adhesion, and susceptibility to apoptosis influence the dynamics of cell size and growth in multicellular environments.