Torque-based immune cell chemotaxis in complex environments

Abstract Directed migration in chemical gradients is crucial to the immune response, yet how immune cells navigate complex tissues remains incompletely understood. Using in vitro migration assays and theoretical modeling, we uncover distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). DCs actively steer toward chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias movement by modulating angular noise and speed. A quantitative Fokker–Planck framework decomposes these behaviors into deterministic and stochastic components. Cytoskeletal perturbations show that microtubules enable torque-based navigation in DCs in collagen gels, whereas actomyosin contractility is required for noise modulation employed by neutrophils and DCs in 2D confined migration assays. Despite both achieving directed migration, the two strategies result in opposing macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. These results reveal distinct navigation aligned with immune function and demonstrate that immune cell chemotaxis is tuned by cytoskeletal architecture and environmental context.