Clustering and ordering in cell assemblies with generic asymmetric aligning interactions

TL;DR

This paper combines experiments and theory to show that asymmetric cell interactions, like contact inhibition of locomotion, prevent large-scale cell clustering and ordering, resulting in finite-sized clusters or dispersed states.

Contribution

It introduces a minimal asymmetric aligning interaction model that captures CIL phenomenology and predicts the suppression of large-scale clustering in active cellular systems.

Findings

Asymmetric interactions reproduce CIL behavior.

Large scale clustering is suppressed by asymmetric alignment.

Finite-sized clusters emerge instead of large-scale order.

Abstract

Collective cell migration plays an essential role in various biological processes, such as development or cancer proliferation. While cell-cell interactions are clearly key determinants of collective cell migration -- in addition to individual cells self-propulsion -- the physical mechanisms that control the emergence of cell clustering and collective cell migration are still poorly understood. In particular, observations have shown that binary cell-cell collisions generally lead to anti-alignement of cell polarities and separation of pairs -- a process called contact inhibition of locomotion (CIL), which is expected to disfavor the formation of large scale cell clusters with coherent motion. Here, we adopt a joint experimental and theoretical approach to determine the large scale dynamics of cell assemblies from elementary pairwise cell-cell interaction rules. We quantify experimentally binary cell-cell interactions and show that they can be captured by a minimal equilibrium-like pairwise asymmetric aligning interaction potential that reproduces the CIL phenomenology. We identify its symmetry class, build the corresponding active hydrodynamic theory and show on general grounds that such asymmetric aligning interaction destroys large scale clustering and ordering, leading instead to a liquid-like microphase of cell clusters of finite size and short lived polarity, or to a fully dispersed isotropic phase. Finally, this shows that CIL-like asymmetric interactions in cellular systems -- or general active systems -- control cluster sizes and polarity, and can prevent large scale coarsening and long range polarity, except in the singular regime of dense confluent systems.