Dense active matter model of motion patterns in confluent cell monolayers

Silke Henkes,J Martin Collinson,Rastko Sknepnek,Eric Bertin,Kaja Kostanjevec

doi:10.1038/s41467-020-15164-5

Abstract

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations. We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. Simulations and normal mode analysis perfectly match when tissue-level reorganisation occurs on times longer than the persistence time of cell motility. Our analytical model quantitatively matches measured velocity correlation functions over more than a decade with a single fitting parameter.

Highlights

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics
We show that the cell-level heterogeneity, that is variations in size, shape, mechanical properties or motility between individual cells of the same type inherent to any cell monolayer, together with individual, persistent, cell motility and soft elastic repulsion between neighbouring cells leads to correlation patterns in the cell motion, with correlation lengths exceeding ten or more cell sizes
Using numerical simulations of models for cell sheets, including a soft disk model as well as a self-propelled Voronoi model (SPV)[37,38], we show that our analytical model provides an excellent match for both types of simulations up to a point where substantial flow in the sheet begins to subtly alter the correlation functions (Fig. 1b)

Summary

Introduction

Epithelial cell monolayers show remarkable displacement and velocity correlations over distances of ten or more cell sizes that are reminiscent of supercooled liquids and active nematics. We show that many observed features can be described within the framework of dense active matter, and argue that persistent uncoordinated cell motility coupled to the collective elastic modes of the cell sheet is sufficient to produce swirl-like correlations We obtain this result using both continuum active linear elasticity and a normal modes formalism, and validate analytical predictions with numerical simulations of two agent-based cell models, soft elastic particles and the self-propelled Voronoi model together with in-vitro experiments of confluent corneal epithelial cell sheets. By tuning the motility and internal properties of individual cells, e.g. cell shape[37,38,39] or cell–cell adhesion[40], a living system can drive itself across this transition and rather accurately control cell motion within the sheet This establishes a picture in which tissue-level patterning is not solely determined by biochemistry (e.g. the distribution of morphogens) but is driven by mechanical cues. Our approach generalises their result for cell–substrate dissipation, and we recover both the scaling results and find quantitative agreement with the experiments presented in ref. 40

Methods

Results

Conclusion