Multi-scale modeling of a wound-healing cell migration assay

A continuum model and a discrete model are developed to capture the population-scale and cell-scale behavior in a wound-healing cell migration assay created from a scrape wound in a confluent cell monolayer. During wound closure, the cell population forms a sustained traveling wave, with close contact between cells behind the wavefront. Cells exhibit contact inhibition of migration and coptact-limited proliferation. The continuum model includes the two dominant mechanisms and characteristics of cell migration and proliferation, using a cell diffusivity function that decreases with cell density and a logistic proliferative growth term. The discrete model arises naturally from the continuum model. Individual cells are simulated as continuous-time random walkers with nearest-neighbor transitions, together with a birth/death process. The migration and proliferation parameters are determined by analysing individual mice 3T3 fibroblast cell trajectories obtained during the development of a confluent cell monolayer and in a wound healing assay. The population-scale model successfully predicts the shape and speed of the traveling wave, while the discrete model is also successful in capturing the contact inhibition of migration effects. (c) 2006 Elsevier Ltd. All rights reserved.