Physical Models of Collective Cell Migration

Abstract

Collective cell migration is a key driver of embryonic development, wound healing, and some types of cancer invasion. Here we provide a physical perspective of the mechanisms underlying collective cell migration. We begin with a catalogue of the cell-cell and cell-substrate interactions that govern cell migration, which we classify into positional and orientational interactions. We then review the physical models that have been developed to explain how these interactions give rise to collective cellular movement. These models span the sub-cellular to the supracellular scales, and they include lattice models, phase fields models, active network models, particle models, and continuum models. For each type of model, we discuss its formulation, its limitations, and the main emergent phenomena that it has successfully explained. These phenomena include flocking and fluid-solid transitions, as well as wetting, fingering, and mechanical waves in spreading epithelial monolayers. We close by outlining remaining challenges and future directions in the physics of collective cell migration.

Spatiotemporal force and motion in collective cell migration

“…For example, experimental observations that collective cell groups move in larger clusters as cell number density is increased [23][24][25][26] later inspired theoretical models to investigate the effect of density on collective migration 10,11,14,19 . Additional examples of connections between theory and experiment are given in recent review articles [27][28][29] .…”

Scalar Active Mixtures: The Nonreciprocal Cahn-Hilliard Model

“…The study of active matter [1,2] has by now permeated across many scientific fields, length scales, and timescales, ranging from the study of catalytic enzymes [3][4][5] and the cytoskeleton [6] inside cells, to the collective motion of cells in tissues [7] and suspensions of bacteria [8,9], all the way to the flocking of birds [10,11]. Throughout the years, particular attention has been given to mechanisms that manifestly break equilibrium physics already at the level of single constituents, as is the case for self-propelled agents such as microswimmers in polar active matter, for the extensile and contractile activity of the constituents in nematic active matter, or for the growth and division in living matter.…”

Mechanical Oscillations in 2D Collective Cell Migration: The Elastic Turbulence

“…These cooperative motions are driven by active cellular forces, but the physical nature of these forces and how they generate elastic waves remain poorly understood. However, it is well-known that generation of waves and their transfer strongly depends on the state of cell-cell junctions and contractility [2,3,16,17]. Most of the works on generation of mechanical waves within cell monolayers have been carried out on fibroblasts, which develop weaker cell-cell adhesions [5].…”