A Rho-GTPase based model explains group advantage in collective chemotaxis of neural crest cells

摘要

A cluster of neural crest cells (NCCs) may chemotax up a shallow external gradient to which a single cell is unresponsive. To explain this intriguing 'group advantage', we propose a chemo-mechanical model based on the signaling proteins Rac1 and RhoA. We represent each cell as a polygon with nodes connected by elastic membranes. Via reaction-diffusion on the membrane and exchange with their cytosolic pools, Rac1 and RhoA interact to produce cell polarization and repolarization subject to random noise. Mechanically, we represent cell motility via overdamped nodal motion subject to passive elastic membrane forces and active protrusive or contractile forces where Rac1 or RhoA dominates. The model reproduces the random walk of a single cell in a weak gradient and two modes of cell-cell interaction: contact inhibition of locomotion and co-attraction. The simultaneous action of contact inhibition and co-attraction suppresses random Rac1 bursts on the membrane and serves to preserve existing protrusions. This amounts to an emergent persistence of polarity that markedly enhances the ability of a cluster of NCCs to chemotax in a weak gradient against random noise, thereby giving rise to the group advantage.