Effects of cell-cell adhesion on collective migration of multicellular clusters*

Collections of cells exhibit directional coherent migration during morphogenesis, cancer-metastasis, and wound healing. Often during migration, bigger clusters split, smaller sub-clusters collide and reassemble, and gaps continually emerge. This leads to the formation of protrusions by some inner cells which eventually act as “leaders", along with the cells at the leading edge, pulling the cluster towards the favorable direction. Large populations like neural crest cells are known to exhibit such phenomena. We hypothesize that the cells may have an optimal adhesion among themselves, rather than very strong or weak, to favor the formation of gaps and achieve an effective faster migration. We test this hypothesis for one- and two-dimensional cell clusters that collectively track chemical gradients using a mechanism based on contact inhibition of locomotion. We develop both a minimal framework based on the lattice gas model of statistical physics, as well as a more realistic framework based on the cellular Potts model. Results from both frameworks support our hypothesis, suggesting that intermediate adhesion leads to optimal migration. We discuss the mechanisms behind this optimum and relate our results to specific cellular systems.