Simultaneous polymerization and adhesion under hypoxia in sickle cell disease
Abstract
Patients with sickle cell disease (SCD) suffer from painful vasoocclusive crises. Polymerization of sickle hemoglobin (HbS) in RBCs is generally considered a major contributor to such crisis events. Here, we present the simultaneous and synergistic coupling of adhesion and HbS polymerization. We show that the age of RBCs in circulation plays an important role in mediating this synergistic effect on blood rheology and clinical symptoms. In particular, the youngest RBCs exhibit unique adhesion dynamics, whereby polymerized HbS fiber bundles grow from cell surfaces to serve as sites of cytoadherence. Our molecular-level simulations show how the attachment and dissociation of molecular bonds influence adhesion dynamics. These results provide a framework that could elucidate the mechanistic basis of SCD vasoocclusive pain crises.
- Publication:
-
Proceedings of the National Academy of Science
- Pub Date:
- September 2018
- DOI:
- 10.1073/pnas.1807405115
- Bibcode:
- 2018PNAS..115.9473P