Spatial Segregation Across Travelling Fronts in Individual-Based and Continuum Models for the Growth of Heterogeneous Cell Populations.

We consider a partial differential equation model for the growth of heterogeneous cell populations subdivided into multiple distinct discrete phenotypes. In this model, cells preferentially move towards regions where they are less compressed, and thus their movement occurs down the gradient of the cellular pressure. The cellular pressure is defined as a weighted sum of the densities (i.e. the volume fractions) of cells with different phenotypes. To translate into mathematical terms the idea that cells with distinct phenotypes have different morphological and mechanical properties, both the cell mobility and the weighted amount the cells contribute to the cellular pressure vary with their phenotype. We formally derive this model as the continuum limit of an on-lattice individual-based model, where cells are represented as single agents undergoing a branching biased random walk corresponding to phenotype-dependent and pressure-regulated cell division, death, and movement. Then, we study travelling wave solutions whereby cells with different phenotypes are spatially segregated across the invading front. Finally, we report on numerical simulations of the two models, demonstrating excellent agreement between them and the travelling wave analysis. The results presented here indicate that inter-cellular variability in mobility can support the maintenance of spatial segregation across invading fronts, whereby cells with a higher mobility drive invasion by occupying regions closer to the front edge.