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Theoretical Simulation of Red Cell Sickling Upon Deoxygenation Based on the Physical Chemistry of Sickle Hemoglobin Fiber Formation
journal contribution
posted on 2018-09-04, 00:00 authored by Emily
B. Dunkelberger, Belhu Metaferia, Troy Cellmer, Eric R. HenryThe polymerization of the mutant
hemoglobin S upon deoxygenation
to form fibers in red blood cells of patients suffering from sickle-cell
anemia results in changes in cell shape and rigidity, also known as
sickling, which underlie the pathology of the disease. While much
has been learned about the fundamental physical chemistry of the polymerization
process, transferring these insights to sickling of red cells under in vivo conditions requires being able to monitor, and ultimately
predict, the time course of cellular sickling under physiological
conditions of deoxygenation. To this end, we have developed an experimental
technique for tracking the temporal evolution of the sickling of red
blood cells under laboratory deoxygenation conditions, based on the
automated analysis of sequences of microscope images and machine-learning
analysis to characterize cell morphology. As an aid in the quantitative
understanding of these experiments, we have developed a computational
framework for simulating the time dependence of sickling in populations
of red blood cells which incorporates the current theoretical and
empirical understanding of the physical chemistry of the sickling
process. In order to apply these techniques to our experiments, we
have theoretically determined the time course of deoxygenation by
solving the diffusion equation for oxygen in our experimental geometry.
With this combined description, we are able to reproduce our experimentally
observed kinetics of sickling, suggesting that our theoretical approach
should be applicable to physiological deoxygenation scenarios.