Enhanced persistence and collective migration in cooperatively aligning cell clusters

TL;DR

This study investigates how small clusters of cells move collectively, revealing that increasing cluster size enhances persistence and collective migration efficiency, with implications for development and cancer metastasis.

Contribution

The paper introduces a combined modeling and theoretical framework to analyze how cluster size influences motility, highlighting the role of cooperation and cell alignment in enhancing migration.

Findings

Cluster persistence time increases with number of cells N.

Intrinsic diffusivity decreases as N increases.

Small clusters exhibit more effective durotaxis than single cells.

Abstract

Most cells possess the capacity to locomote. Alone or collectively, this allows them to adapt, to rearrange, and to explore their surroundings. The biophysical characterization of such motile processes, in health and disease, has so far focused mostly on two limiting cases: single-cell motility on the one hand, and the dynamics of confluent tissues such as the epithelium on the other. The in-between regime of clusters, composed of relatively few cells, moving as a coherent unit has received less attention. Such small clusters are, however, deeply relevant in development but also in cancer metastasis. In this work, we use cellular Potts models and analytical active matter theory to understand how the motility of small cell clusters changes with N, the number of cells in the cluster. Modeling and theory reveal our two main findings: Cluster persistence time increases with N while the intrinsic diffusivity decreases with N. We discuss a number of settings in which the motile properties of more complex clusters can be analytically understood, revealing that the focusing effects of small-scale cooperation and cell-cell alignment can overcome the increased bulkiness and internal disorder of multicellular clusters to enhance overall migrational efficacy. We demonstrate this enhancement for small-cluster collective durotaxis, which is shown to proceed more effectively than for single cells. Our results may provide some novel insights into the connection between single-cell and large-scale collective motion and may point the way to the biophysical origins of the enhanced metastatic potential of small tumor cell clusters.