# Frustration induced phases in migrating cell clusters

## TL;DR

This study investigates the complex collective motion phases of migrating cell clusters, revealing how local environmental heterogeneity and cell motility influence phase transitions, with implications for understanding physiological and pathological processes.

## Contribution

The paper introduces a novel agent-based model explaining the coexistence of multiple motion phases in cell clusters, aligning well with experimental observations and predicting phase behavior based on cluster size and chemical gradients.

## Key findings

- Coexistence of translational, rotational, and random phases in cell clusters.
- Transitions driven by competition between ordered rim and disordered core.
- Model predictions match experimental data on phase dependence on size and gradients.

## Abstract

Collective motion of cells is common in many physiological processes, including tissue development, repair, and tumor formation. Recent experiments have shown that certain malignant cancer cells form clusters in a chemoattractant gradient, which display three different phases of motion: translational, rotational, and random. Intriguingly, all three phases are observed simultaneously, with clusters spontaneously switching between these modes of motion. The origin of this behavior is not understood at present, especially the robust appearance of cluster rotations. Guided by experiments on the motion of two-dimensional clusters in-vitro, we developed an agent based model in which the cells form a cohesive cluster due to attractive and alignment interactions but with potentially different behaviors based on their local environment. We find that when cells at the cluster rim are more motile, all three phases of motion coexist, in excellent agreement with the observations. Using the model we can identify that the transitions between different phases are driven by a competition between an ordered rim and a disordered core accompanied by the creation and annihilation of topological defects in the velocity field. The model makes definite predictions regarding the dependence of the motility phase of the cluster on its size and external chemical gradient, which agree with our experimental data. Our results suggest that heterogeneous behavior of individuals, based on local environment, can lead to novel, experimentally observed phases of collective motion.