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

TL;DR

This paper investigates how clusters of cells can collectively sense and move toward chemical signals through mechanisms like adaptation, amplification, and co-attraction, revealing new insights into their guidance strategies without relying on strong adhesion.

Contribution

It introduces a computational model showing that collective guidance can occur via co-attraction without persistent cell contacts, highlighting the roles of adaptation and amplification in cluster chemotaxis.

Findings

Cluster speed varies non-monotonically with size under LEGI sensing.

Collective guidance is possible without strong cell-cell adhesion, relying on co-attraction.

Cluster behaviors like rotation can emerge from co-attraction mechanisms.

Abstract

Single eukaryotic cells commonly sense and follow chemical gradients, performing chemotaxis. Recent experiments and theories, however, show that even when single cells do not chemotax, clusters of cells may, if their interactions are regulated by the chemoattractant. We study this general mechanism of "collective guidance" computationally with models that integrate stochastic dynamics for individual cells with biochemical reactions within the cells, and diffusion of chemical signals between the cells. We show that if clusters of cells use the well-known local excitation, global inhibition (LEGI) mechanism to sense chemoattractant gradients, the speed of the cell cluster becomes non-monotonic in the cluster's size - clusters either larger or smaller than an optimal size will have lower speed. We argue that the cell cluster speed is a crucial readout of how the cluster processes chemotactic signal; both amplification and adaptation will alter the behavior of cluster speed as a function of size. We also show that, contrary to the assumptions of earlier theories, collective guidance does not require persistent cell-cell contacts and 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 collective guidance that is robust to varying chemoattractant concentrations while not requiring strong cell-cell adhesion.