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Rapid and Inefficient Kinetics of Sickle Hemoglobin Fiber Growth
source: Science Advances
year: 2019
authors: Castle BT, Odde DJ, Wood DK
summary/abstract:In sickle cell disease, the aberrant assembly of hemoglobin fibers induces changes in red blood cell morphology and stiffness, which leads to downstream symptoms of the disease. Therefore, understanding of this assembly process will be important for the treatment of sickle cell disease. By performing the highest spatiotemporal resolution measurements (55 nm at 1 Hz) of single sickle hemoglobin fiber assembly to date and combining them with a model that accounts for the multistranded structure of the fibers, we show that the rates of sickle hemoglobinaddition and loss have been underestimated in the literature by at least an order of magnitude.
These results reveal that the sicklehemoglobin self-assembly process is very rapid and inefficient (4% efficient versus 96% efficient based on previous analyses), where net growth is the small difference between over a million addition-loss events occurring every second.
organization: University of Minnesota, USADOI: 10.1126/sciadv.aau1086
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