Spatial Confinement and Temporal Dynamics of Selectin Ligands Enable Stable Hematopoietic Stem Cell Rolling

Abstract

Hematopoietic stem/progenitor cell (HSPC) homing is initiated by tethering and rolling of the cells on endothelium through selectin-ligand interactions. Although multiple factors that affect the rolling behavior of the cells have been identified, molecular mechanisms that enable slow and stable cell rolling remain elusive. Here, using a microfluidics-based single-molecule live cell fluorescence imaging, we reveal that unique spatiotemporal dynamics of selectin ligands on the membrane tethers and slings, which are distinct from that on the cell body, play an essential role in the rolling of the cell. Our results suggest that the spatial confinement of the selectin ligands to the tethers and slings together with the rapid scanning of a large area by the selectin ligands increases the efficiency of selectin-ligand interactions during cell rolling, resulting in slow and stable rolling of the cell on the selectins. Our findings provide novel insights and contribute significantly to the molecular-level understanding of the initial and essential step of the homing.