Abstract
Erythrocytes from sickle cell trait (SCT) patients aggregate during strenuous exercise, resulting in inflammation, blood flow impairment, and vaso-occlusive events. While the exact role of exercise conditions and how they lead to complications is virtually unknown, it likely occurs because of their adhesive interactions with the extracellular matrix (ECM) and endothelial cells (ECs), irregular viscoelastic properties, and morphology. The current study employs single-molecule atomic force microscopy (AFM) experiments to quantitatively measure the frequency and bond strength of SCT erythrocytes with ECM laminin α5 and endothelial αvβ3. Epinephrine, a hormone secreted during stressful conditions, is administered in vitro to determine its direct effect on SCT adhesion. In the presence of epinephrine, we measured an increase in the frequency of adhesion events of BCAM/Lu and LW expressed on the SCT erythrocyte surface with ECM laminin α5 and endothelial αvβ3, respectively. The observed clustering of BCAM/Lu and LW receptors into nanodomains explains the measured amplification in bond strength. In conclusion, we found that epinephrine modulates the BCAM/Lu-laminin α5 and LW-αvβ3 bond interactions. The measured increases in adhesion frequency and bond strength suggest that epinephrine contributes to the pathophysiology of vaso-occlusive sequelae related to sudden death in SCT individuals during strenuous exercise.
Published Version
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