Modeling tumor cell migration: from microscopic to macroscopic

TL;DR

This paper derives a nonlinear diffusion PDE from microscopic models of tumor cell migration with contact interactions, linking cellular behavior to macroscopic tumor growth predictions validated by experiments.

Contribution

It introduces a multiscale approach to connect microscopic contact interactions with a macroscopic nonlinear diffusion model for tumor cell migration.

Findings

Derived a nonlinear diffusion PDE from microscopic models.

Explicitly related diffusivity to cell density and interaction parameters.

Validated the PDE model against numerical simulations and in vitro experiments.

Abstract

It has been shown experimentally that contact interactions may influence the migration of cancer cells. Previous works have modelized this thanks to stochastic, discrete models (cellular automata) at the cell level. However, for the study of the growth of real-size tumors with several millions of cells, it is best to use a macroscopic model having the form of a partial differential equation (PDE) for the density of cells. The difficulty is to predict the effect, at the macroscopic scale, of contact interactions that take place at the microscopic scale. To address this we use a multiscale approach: starting from a very simple, yet experimentally validated, microscopic model of migration with contact interactions, we derive a macroscopic model. We show that a diffusion equation arises, as is often postulated in the field of glioma modeling, but it is nonlinear because of the interactions. We give the explicit dependence of diffusivity on the cell density and on a parameter governing cell-cell interactions. We discuss in details the conditions of validity of the approximations used in the derivation and we compare analytic results from our PDE to numerical simulations and to some in vitro experiments. We notice that the family of microscopic models we started from includes as special cases some kinetically constrained models that were introduced for the study of the physics of glasses, supercooled liquids and jamming systems.