Leader cells in collective chemotaxis: Optimality and trade-offs

Clusters of cells can work together in order to follow a signal gradient, chemotaxing even when single cells do not. Cells in different regions of collectively migrating neural crest streams show different gene expression profiles, suggesting that cells may specialize to leader and follower roles. We use a minimal mathematical model to understand when this specialization is advantageous. In our model, leader cells sense the gradient with an accuracy that depends on the kinetics of ligand-receptor binding, while follower cells follow the cluster's direction with a finite error. Intuitively, specialization into leaders and followers should be optimal when a few cells have more information than the rest of the cluster, such as in the presence of a sharp transition in chemoattractant concentration. We do find this-but also find that high levels of specialization can be optimal in the opposite limit of very shallow gradients. We also predict that the best location for leaders may not be at the front of the cluster. In following leaders, clusters may have to choose between speed and flexibility. Clusters with only a few leaders can take orders of magnitude more time to reorient than all-leader clusters.