Juliane Zimmermann | Searcharxiv

arXiv2015

Emergent collective chemotaxis without single-cell gradient sensing

Many eukaryotic cells chemotax, sensing and following chemical gradients. However, experiments have shown that even under conditions when single cells cannot chemotax, small clusters may still follow a gradient. This behavior has been observed in neural crest cells, in lymphocytes, and during border cell migration in Drosophila, but its origin remains puzzling. Here, we propose a new mechanism underlying this "collective guidance", and study a model based on this mechanism both analytically and computationally. Our approach posits that the contact inhibition of locomotion (CIL), where cells polarize away from cell-cell contact, is regulated by the chemoattractant. Individual cells must measure the mean attractant value, but need not measure its gradient, to give rise to directional motility for a cell cluster. We present analytic formulas for how cluster velocity and chemotactic index depend on the number and organization of cells in the cluster. The presence of strong orientation effects provides a simple test for our theory of collective guidance.

physics.bio-ph↗

arXiv2015

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

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.

q-bio.CB↗