, Volume 71, Issue 5, pp 1117-1147

Continuous Models for Cell Migration in Tissues and Applications to Cell Sorting via Differential Chemotaxis

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Abstract

Chemotaxis, the guided migration of cells in response to chemical gradients, is vital to a wide variety of biological processes, including patterning of the slime mold Dictyostelium, embryonic morphogenesis, wound healing, and tumor invasion. Continuous models of chemotaxis have been developed to describe many such systems, yet few have considered the movements within a heterogeneous tissue composed of multiple subpopulations. In this paper, a partial differential equation (PDE) model is developed to describe a tissue formed from two distinct chemotactic populations. For a “crowded” (negligible extracellular space) tissue, it is demonstrated that the model reduces to a simpler one-species system while for an “uncrowded” tissue, it captures both movement of the entire tissue (via cells attaching to/migrating within an extracellular substrate) and the within-tissue rearrangements of the separate cellular subpopulations. The model is applied to explore the sorting of a heterogeneous tissue, where it is shown that differential-chemotaxis not only generates classical sorting patterns previously seen via differential-adhesion, but also demonstrates new classes of behavior. These new phenomena include temporal dynamics consisting of a traveling wave composed of spatially sorted subpopulations reminiscent of Dictyostelium slugs.