Individual-based and continuum models of phenotypically heterogeneous growing cell populations

Abstract

<abstract> <p>Existing comparative studies between individual-based models of growing cell populations and their continuum counterparts have mainly been focused on homogeneous populations, in which all cells have the same phenotypic characteristics. However, significant intercellular phenotypic variability is commonly observed in cellular systems. In light of these considerations, we develop here an individual-based model for the growth of phenotypically heterogeneous cell populations. In this model, the phenotypic state of each cell is described by a structuring variable that captures intercellular variability in cell proliferation and migration rates. The model tracks the spatial evolutionary dynamics of single cells, which undergo pressure-dependent proliferation, heritable phenotypic changes and directional movement in response to pressure differentials. We formally show that the continuum limit of this model comprises a non-local partial differential equation for the cell population density function, which generalises earlier models of growing cell populations. We report on the results of numerical simulations of the individual-based model which illustrate how proliferation-migration tradeoffs shaping the evolutionary dynamics of single cells can lead to the formation, at the population level, of travelling waves whereby highly-mobile cells locally dominate at the invasive front, while more-proliferative cells are found at the rear. Moreover, we demonstrate that there is an excellent quantitative agreement between these results and the results of numerical simulations and formal travelling-wave analysis of the continuum model, when sufficiently large cell numbers are considered. We also provide numerical evidence of scenarios in which the predictions of the two models may differ due to demographic stochasticity, which cannot be captured by the continuum model. This indicates the importance of integrating individual-based and continuum approaches when modelling the growth of phenotypically heterogeneous cell populations.</p> </abstract>