Chemo-mechanical Diffusion Waves Orchestrate Collective Oscillations of Immune Cell Podosomes

Dendritic cells utilize podosomes, actin-rich protrusions, to migrate in tissues and patrol for foreign antigens. Individual podosomes show protrusion and retraction cycles (vertical oscillations) to probe underlying matrices, while multiple podosomes arranged in clusters exhibit coordinated wave-like spatiotemporal dynamics. However, the mechanism linking vertical oscillations and wave-like dynamics remains unclear. Here we develop a chemo-mechanical model for both oscillatory growth of individual podosomes and wave-like dynamics in podosome clusters. We found that podosomes oscillate when actin polymerization-associated protrusion and signaling-associated myosin contraction occur at similar rates; actin diffusion within clusters drives wave-like dynamics. By quantifying and comparing the wavelength, frequency, and speed of wave dynamics in experiments and simulations, we validated our model by predicting the impact of different drug treatments and substrate stiffness on podosome dynamics. The integrated theoretical and experimental approach reveals the mechanism of podosome dynamics and sheds light on podosomes' roles in immune cell mechanosensing and mechanotransduction.