Mechanical control of cell proliferation patterns in growing epithelial monolayers

Biophys J. 2024 Mar 6:S0006-3495(24)00167-X. doi: 10.1016/j.bpj.2024.03.002. Online ahead of print.ABSTRACTCell proliferation plays a crucial role in regulating tissue homeostasis and development. However, our understanding of how cell proliferation is controlled in densely packed tissues is limited. Here we develop a computational framework to predict the patterns of cell proliferation in growing epithelial tissues, connecting single-cell behaviors and cell-cell interactions to tissue-level growth. Our model incorporates probabilistic rules governing cell growth, division, and elimination, while also taking into account their feedback with tissue mechanics. In particular, cell growth is suppressed and apoptosis is enhanced in regions of high cell density. With these rules and model parameters calibrated using experimental data for MDCK epithelial monolayers, we predict how tissue confinement influences cell size and proliferation dynamics, and how single-cell physical properties influence the spatiotemporal patterns of tissue growth. In this model, mechanical feedback between tissue confinement and cell growth leads to enhanced cell proliferation at tissue boundaries, whereas cell growth in the bulk is arrested, recapitulating experimental observations in epithelial tissues. By tuning cellular elasticity and contact inhibition of proliferation we can regulate the emergent patterns of cell proliferation, ranging from uniform growth at low contact inhibition to localized growt...

Source: Biophysical Journal - March 7, 2024 Category: Physics Authors: Logan C Carpenter Fernanda P érez-Verdugo Shiladitya Banerjee Source Type: research