Discrete and continuous mathematical models of sharp-fronted collective cell migration and invasion

Abstract

Mathematical models describing the spatial spreading and invasion of populations of biological cells are often developed in a continuum modelling framework using reaction-diffusion equations. While continuum models based on linear diffusion are routinely employed and known to capture key experimental observations, linear diffusion fails to predict well-defined sharp fronts that are often observed experimentally. This observation has motivated the use of nonlinear degenerate diffusion, however these nonlinear models and the associated parameters lack a clear biological motivation and interpretation. Here we take a different approach by developing a stochastic discrete lattice-based model incorporating biologically-inspired mechanisms and then deriving the reaction-diffusion continuum limit. Inspired by experimental observations, agents in the simulation deposit extracellular material, that we call a substrate, locally onto the lattice, and the motility of agents is taken to be proportional to the substrate density. Discrete simulations that mimic a two--dimensional circular barrier assay illustrate how the discrete model supports both smooth and sharp-fronted density profiles depending on the rate of substrate deposition. Coarse-graining the discrete model leads to a novel partial differential equation (PDE) model whose solution accurately approximates averaged data from the discrete model. The new discrete model and PDE approximation provides a simple, biologically motivated framework for modelling the spreading, growth and invasion of cell populations with well-defined sharp frontsComment: 47 Pages, 8 Figure