  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.
