Different Ways Through the Maze: Immune Cell Chemotaxis in Complex Environments

Theresa Jakuszeit

Directed migration in response to chemical gradients is central to the immune response, yet how immune cells navigate complex tissue architectures remains incompletely understood. In this talk, I will focus on high-resolution in vitro experiments with theoretical modeling, which revealed distinct chemotactic strategies in two key immune cell types: neutrophils and dendritic cells (DCs). Tracking single-cell trajectories in controlled 3D collagen matrices, we found that DCs orient up chemokine gradients via a deterministic torque-like reorientation, while neutrophils bias their migration through modulation of angular noise and speed. A quantitative Fokker–Planck framework captures these strategies, enabling a decomposition of chemotactic behavior into deterministic and stochastic contributions. Perturbations of cytoskeletal components identified microtubules as essential for torque-based navigation in DCs, whereas actomyosin contractility is required for noise modulation in neutrophils. These strategies manifest in distinct macroscopic outcomes: torque-driven cells minimize dispersion, while noise-biased migration enhances population spread. Finally, I will discuss these observations in the context of directed migration of immune cell collectives, including swarming and jamming phenomena.