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Single eukaryotic cells commonly sense and follow chemical gradients,performing chemotaxis. Recent experiments and theories, however, show that evenwhen single cells do not chemotax, clusters of cells may, if their interactionsare regulated by the chemoattractant. We study this general mechanism of"collective guidance" computationally with models that integrate stochasticdynamics for individual cells with biochemical reactions within the cells, anddiffusion of chemical signals between the cells. We show that if clusters ofcells use the well-known local excitation, global inhibition (LEGI) mechanismto sense chemoattractant gradients, the speed of the cell cluster becomesnon-monotonic in the cluster's size - clusters either larger or smaller than anoptimal size will have lower speed. We argue that the cell cluster speed is acrucial readout of how the cluster processes chemotactic signal; bothamplification and adaptation will alter the behavior of cluster speed as afunction of size. We also show that, contrary to the assumptions of earliertheories, collective guidance does not require persistent cell-cell contactsand strong short range adhesion to function. If cell-cell adhesion is absent,and the cluster cohesion is instead provided by a co-attraction mechanism, e.g.chemotaxis toward a secreted molecule, collective guidance may still function.However, new behaviors, such as cluster rotation, may also appear in this case.Together, the combination of co-attraction and adaptation allows for collectiveguidance that is robust to varying chemoattractant concentrations while notrequiring strong cell-cell adhesion.

Collective signal processing in cluster chemotaxis: roles of adaptation, amplification, and co-attraction in collective guidance