Single-molecule imaging and microfluidic platform reveal molecular mechanisms of leukemic cell rolling
byBader Al Alwan, Karmen AbuZineh, Shuho Nozue, aigerim rakhmatulina, Mansour Aldehaiman, Asma S. Al-Amoodi, Maged F. Serag, Fajr A. Aleisa, Jasmeen S. Merzaban, Satoshi Habuchi
Hematopoietic stem/progenitor cell (HSPC) and leukemic cell homing is an
important biological phenomenon that occurs through key interactions
between adhesion molecules. Tethering and rolling of the cells on
endothelium, the crucial initial step of the adhesion cascade, is
mediated by interactions between selectins expressed on endothelium to
their ligands expressed on HSPCs/leukemic cells in flow. Although
multiple factors that affect the rolling behavior of the cells have been
identified, molecular mechanisms that enable the essential 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 process.