Dense active matter model of motion patterns in confluent cell monolayers

Abstract

Epithelial cell monolayers show remarkable long-range displacement and velocity correlations reminiscent of supercooled liquids and active nematics. Here we show that many of the observed features can be understood within the framework of active matter at high densities. In particular, we argue that uncoordinated but persistent cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce characteristic swirl-like correlations. This includes a divergent correlation length in the limit of infinite persistence time. We derive this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based models of soft elastic particles and in-vitro experiments of confluent corneal epithelial cell sheets. Our analytical model is able to fit measured velocity correlation functions without any free parameters. SIGNIFICANCEUnderstanding how cells in confluent epithelial sheets coordinate to create coherent motion patterns is a central question in cell and developmental biology. We show that a simple active matter model that couples crawling of an individual cell to the elastic environment provided by the surrounding cells, faithfully captures large-scale coherent motion patterns observed in the epithelial cell monolayers. The linear elastic model can be analyzed analytically and is able to match numerical simulations of two complementary models without any fitting parameters. It is a good match for experiments on corneal epithelial cells.

Time-dependent properties of interacting active matter: Dynamical behavior of one-dimensional systems of self-propelled particles

“…A nonequilibrium phase activity-density diagram has been introduced to represent both homogeneous and inhomogeneous regimes [34] and the structural properties of the system have been compared with the typical size of the aligned domains. The model reproduces several experimental results regarding confluent cell monolayers [35][36][37][38], whose velocity fields display alignment patterns quite similar to the corresponding predictions of the ABP model. Hence, even such a simple model can account for the phenomenology of active matter systems at high density observed in experiments.…”

In primary airway epithelial cells, the unjamming transition is distinct from the epithelial-to-mesenchymal transition

“…Data presented in b and d are mean ± SD for n = 7–20 independent simulations for each datapoint. e Increasing the single cell persistence length l 0 (in units of the average cell diameter, see Supplementary Methods) at constant p 0 = 4 and v 0 = 1.2 leads to the emergence of growing migrating packs (vii–ix) 92 , 126 . Single cell velocity is represented as a vector; the largest pack is highlighted.…”

Extreme active matter at high densities

“…2), over the range of τ p values investigated. This deviation from equipartition may be due to the fact that the joint distribution of velocities and positions at steady state does not decouple 2,26 .…”

“…Promising candidates for extreme active matter are monolayers of persistently motile cells; indeed, Garcia et al 40 observe jammingyielding behaviour in such monolayers of epithelial cells. A model similar to the one considered here has been used in a recent study 26 of motion patterns in confluent cell monolayers. Recent experiments 41,42 on dense systems of Janus colloids have provided a physical realisation of dense active matter near the glass transition.…”