Collective cell migration due to guidance-by-followers is robust to multiple stimuli

Abstract

Collective cell migration is an important process during biological development and tissue repair but may turn malignant during tumor invasion. Mathematical and computational models are essential to unravel the mechanisms of self-organization that underlie the emergence of collective migration from the interactions among individual cells. Recently, guidance-by-followers was identified as one such underlying mechanism of collective cell migration in the embryo of the zebrafish. This poses the question of how the guidance stimuli are integrated when multiple cells interact simultaneously. In this study, we extend a recent individual-based model by an integration step of the vectorial guidance stimuli and compare model predictions obtained for different variants of the mechanism (arithmetic mean of stimuli, dominance of stimulus with largest transmission interface, and dominance of most head-on stimulus). Simulations are carried out and quantified within the modeling and simulation framework Morpheus. Collective cell migration is found to be robust and qualitatively identical for all considered variants of stimulus integration. Moreover, this study highlights the role of individual-based modeling approaches for understanding collective phenomena at the population scale that emerge from cell-cell interactions.