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.
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.
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.
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