Branched networks constitute a ubiquitous structure in biology, arising in plants, lungs, and the circulatory system; however, the mechanisms behind their creation are not well understood. A commonly used model for network morphogenesis proposes that sprouts develop through interactions between leader (tip) cells and follower (stalk) cells. In this description, tip cells emerge from existing structures, travel up chemoattractant gradients, and form new networks by guiding the movement of stalk cells. Such dynamics have been mathematically represented by continuum “snail-trail” models in which the tip cell flux contributes to the stalk cell proliferation rate. Although snail-trail models constitute a classical depiction of leader-follower behavior, their accuracy has yet to be evaluated in a rigorous quantitative setting. Here, we extend the snail-trail modeling framework to two spatial dimensions by introducing a novel multiplicative factor to the stalk cell rate equation, which corrects for neglected network creation in directions other than that of the migrating front. Our derivation of this factor demonstrates that snail-trail models are valid descriptions of cell dynamics when chemotaxis dominates cell movement. We confirm that our snail-trail model accurately predicts the dynamics of tip and stalk cells in an existing agent-based model (ABM) for network formation [Pillay et al., Phys. Rev. E 95, 012410 (2017)]. We also derive conditions for which it is appropriate to use a reduced, one-dimensional snail-trail model to analyze ABM results. Our analysis identifies key metrics for cell migration that may be used to anticipate when simple snail-trail models will accurately describe experimentally observed cell dynamics in network formation.

• Received 30 June 2020
• Revised 1 October 2020
• Accepted 18 November 2020

DOI:https://doi.org/10.1103/PhysRevE.102.062417