Internal durotaxis and asymmetric shape of cell clusters

Groups of migrating cells are usually guided by external cues, such as gradients of chemoattractant (chemotaxis), substrate stiffness (durotaxis), or electrostatic potential (electrotaxis). Here, I will show that cell groups can also be guided by internal cues, i.e., by gradients of their own properties. We found that, when moving from soft to stiff substrate, clusters of neural crest cells exhibit an opposite gradient in their own tissue stiffness, with soft cells at the front and stiff cells at the back. We predict that this internal stiffness gradient is enough to guide collective cell migration — a phenomenon that we call internal durotaxis. Moreover, these cell clusters are taller at the back than at the front. We explain this asymmetric height profile by modeling the cell cluster as an active liquid droplet driven by the motile cells at its base. We speculate that the emergence of internal guidance cues could provide robustness to the migration of cell clusters in noisy environments.