Chemotactic response induced instabilities and optimal forward migration of multicellular clusters

Collective chemotaxis of multicellular clusters is an important phenomenon in various physiological contexts, ranging from embryonic development to cancer metastasis. These clusters display interesting shape dynamics as well as shape instabilities, but their physical origin and role in overall chemotactic migration still remains unclear. To address this, we employ a cell-based computational model that incorporates adhesive and exclusion interactions between cells, contact inhibition of locomotion, and chemotactic response of single cells. Our findings show that clusters remain fluid and maintain cohesive forward migration at low chemoattractant gradients, below a threshold value. Above this critical gradient, the clusters display an instability that causes them to elongate perpendicular to their direction of motion and eventually break apart. Our model predicts that further increase in the chemoattractant gradient causes a chemotactic response that results in cluster solidification and a significant reduction in forward migration. We compare our results with in vitro data on migrating malignant lymphocyte clusters and demonstrate that our predictions are in good agreement. Understanding these collective mechanisms provides valuable insights into generic instabilities of chemotactic clusters of active particles and cells, the existence of optimal conditions for maximizing forward migration efficiency and physical factors that contribute to metastatic spreading.