A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters

Highlights

• We propose a new mechanism, the persistence of polarity, that enables spontaneous directional collective migration.

• The model predicts neural crest cells migrating collectively down a corridor, in agreement with in vitro experiments.

• Maximum migration efficiency occurs at an optimal corridor width that scales with the square root of the number of cells.

• The model shows the advantage of modeling collective migration from intracellular signaling as opposed to cell-level rules.

Abstract

We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts. This produces persistent directional migration of cell clusters in corridors. Our model confirms a prior hypothesis that co-attraction and contact inhibition are key to spontaneous collective migration, and provides an explanation of their cooperative working mechanism in terms of Rho GTPase signaling. The model shows that the spontaneous migration is more robust for larger clusters, and is most efficient in a corridor of optimal confinement.