Abstract
Collective motions of groups of cells are observed in many biological settings such as embryo development, tissue formation, and cancer metastasis. To effectively model collective cell movement, it is important to incorporate cell specific features such as cell size, cell shape, and cell mechanics, as well as active behavior of cells such as protrusion and force generation, contractile forces, and active biochemical signaling mechanisms that regulate cell behavior. In this paper, we develop a comprehensive model of collective cell migration in confluent epithelia based on the vertex modeling approach. We develop a method to compute cell-cell viscous friction based on the vertex model and incorporate RhoGTPase regulation of cortical myosin contraction. Global features of collective cell migration are examined by computing the spatial velocity correlation function. As active cell force parameters are varied, we found rich dynamical behavior. Furthermore, we find that cells exhibit nonlinear phenomena such as contractile waves and vortex formation. Together our work highlights the importance of active behavior of cells in generating collective cell movement. The vertex modeling approach is an efficient and versatile approach to rigorously examine cell motion in the epithelium.
Highlights
Organized motion of epithelial cells as a group is crucial to developmental processes such as embryo patterning and organ formation.1–3 Epithelia are tissues that form the surface for most organs in the body
We develop a comprehensive model of collective cell migration in confluent epithelia based on the vertex modeling approach
We develop a method to compute cell-cell viscous friction based on the vertex model and incorporate RhoGTPase regulation of cortical myosin contraction
Summary
Organized motion of epithelial cells as a group is crucial to developmental processes such as embryo patterning and organ formation. Epithelia are tissues that form the surface for most organs in the body. In wound healing or tumor invasion, where cells move to cover unfilled gaps, Kim et al showed another model of cell guidance where the cells at the edge exert tractions that pull systematically towards the gap using monolayer stress microscopy.16 In another similar biological context of filling gaps, Rodrıguez-Franco et al. discovered propagation of deformation waves across the monolayer during boundary formation between two cell sheets. We combine the vertex mechanical model with active biochemical signaling control of cell forces. To understand how active contractility, which is dependent on GTPase signaling, works hand in hand with cell shape changes and motion, we incorporated a Rho-Myosin signaling mechanism within our vertex model. The active contractility mechanism generates vortical defects within the coherent streaming These simulation results are consistent with observed collective migration phenomena observed in experiments and suggest that simple models of active cell mechanics without cell-cell communication can explain most of these phenomena
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