Neutrophil Membrane Tether Coalescence: A Novel Mechanoadaptive Response to Abrupt Flow Acceleration

Neutrophils navigating the vasculature encounter regions of abrupt flow acceleration that challenge their adhesive capacity. Here, a previously uncharacterized mechanoadaptive response that enables neutrophils to maintain adhesion under these challenging conditions is revealed. Using microfluidic systems to precisely control flow dynamics, it is demonstrated that neutrophils respond differently to steady versus accelerating flow (delta shear) conditions. While steady‐increasing flow induces formation of multiple discrete tethers, abrupt acceleration triggers their coalescence into thicker, mechanically robust structures that significantly enhance adhesion stability. Through Machine Intelligent Structured Illumination Microscopy with exceptional spatiotemporal resolution, the nanoscale dynamics of this coalescence process is characterized, revealing that despite extensive membrane remodeling, the original anchor points of adhesion molecules remain spatially fixed. Dual‐color spinning total internal reflection fluorescence imaging shows targeted accumulation of F‐actin at the cell tongue, providing critical mechanical support. Differential effects of actin‐disrupting agents confirm that tether coalescence depends on intact cytoskeletal structures rather than active polymerization. This membrane adaptation represents a sophisticated strategy enabling neutrophils to withstand high detachment forces in disturbed flow environments characteristic of vascular bifurcations, stenoses, and device‐associated thromboinflammation. These findings advance understanding of neutrophil mechanobiology and may inform therapeutic strategies targeting pathological neutrophil adhesion without compromising essential immune functions.