Single-molecule imaging and microfluidic platform reveal molecular mechanisms of leukemic cell rolling

Bader Al Alwan, Karmen AbuZineh, Shuho Nozue, Aigerim Rakhmatulina, Mansour M. Aldehaiman, Asma S. Al-Amoodi, Maged F. Serag, Fajr A Aleisa, Jasmeen Merzaban, Satoshi Habuchi

Research output: Contribution to journalArticlepeer-review

Abstract

AbstractHematopoietic 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.
Original languageEnglish (US)
JournalCommunications Biology
Volume4
Issue number1
DOIs
StatePublished - Jul 14 2021

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