Competing chemical gradients change chemotactic dynamics and cell distribution

Abstract

Cells are constantly exposed to diverse stimuli-chemical, mechanical, or electrical-that guide their movement. In physiological conditions, these signals often overlap, as seen during infections, where neutrophils and dendritic cells navigate through multiple chemotactic fields. How cells integrate and prioritize competing signals remains unclear. For instance, in the presence of opposing chemoattractant gradients, how do cells decide which direction to go? When should local signals dominate distant ones? A key factor in these processes is the precision with which cells sense each gradient, which depends non-monotonically on concentrations. Here, we study how gradient sensing accuracy shapes cell navigation in the presence of two distinct chemoattractant sources. We model cells as active random walkers that sense local gradients and combine these estimates to reorient their movement. Our results show that cells sensing multiple gradients can display a range of chemotactic behaviors, including anisotropic spatial patterns and varying degrees of confinement, depending on gradient shape and source location. The model also predicts cases where cells exhibit multistep navigation across sources or a hierarchical response toward one source, driven by disparities in their sensitivity to each chemoattractant. These findings highlight the role of gradient sensing in shaping spatial organization and navigation strategies in multi-field chemotaxis.