Progressive mechanical confinement of chemotactic neutrophils induces arrest, oscillations, and retrotaxis

Neutrophils reach the sites of inflammation and infection in a timely manner by navigating efficiently through mechanically complex interstitial spaces, following the guidance of chemical gradients. However, our understanding of how neutrophils that follow chemical cues overcome mechanical obstacles in their path is restricted by the limitations of current experimental systems. Observations in vivo provide limited insights due to the complexity of the tissue environment. Here, we developed microfluidic devices to study the effect of progressive mechanical confinement on the migration patterns of human neutrophils toward chemical attractants. Using these devices, we identified four migration patterns: arrest, oscillation, retrotaxis, and persistent migration. The proportion of these migration patterns is different in patients receiving immunosuppressant treatments after kidney transplant, patients in critical care, and neonatal patients with infections and is distinct from that in healthy donors. The occurrence of these migration patterns is independent of the nuclear lobe number of the neutrophils and depends on the integrity of their cytoskeletal components. Our study highlights the important role of mechanical cues in moving neutrophils and suggests the mechanical constriction-induced migration patterns as potential markers for infection and inflammation.