Shedding new light on sickle cell disease origins
November 20, 2023 — Scientists now have a better understanding of the mechanisms of sickle cell disease pathology, thanks to a new study from Professor David Wood and PhD student Dillon Williams. Results from the Department of Biomedical Engineering team were published in Proceedings of the National Academy of Sciences (PNAS) this week.
While polymerization of deoxygenated hemoglobin was identified as the origin of sickle cell disease pathology more than 70 years ago, scientists have not fully understood how this molecular event alters red blood cell mechanics and leads to downstream pathology.
In this study, Wood and Williams presented an assay capable of measuring the bulk mechanical changes that occur in red blood cells containing a HbS — a mutated hemoglobin also known sickle hemoglobin — over the full range of physiological oxygen concentrations.
Results demonstrate that red blood cells with detectable levels of HbS polymer are dramatically stiffer than those without polymer. The fraction of red blood cells with detectable polymer increases with decreasing oxygen, but the measured stiffness of these cells is constant across oxygen concentrations.
This suggests that very stiff red blood cells could exist even in highly oxygenated tissues, which could help explain some of the clinical pathology. Additionally, this measurement could be used to help assess the efficacy of new anti-sickling therapies including gene therapy.