Predicting the morphology of sickle red blood cells using coarse-grained models of intracellular aligned hemoglobin polymers.

Sickle red blood cells (SS-RBCs) exhibit heterogeneous cell morphologies (sickle, holly leaf, granular, etc.) in the deoxygenated state due to the polymerization of the sickle hemoglobin. Experimental evidence points to a close relationship between SS-RBC morphology and intracellular aligned hemoglobin polymers. Here, we develop a coarse-grained (CG) stochastic model to represent the growth of the intracellular aligned hemoglobin polymer domain. The CG model is calibrated based on the mechanical properties (Young's modulus, bending rigidity) of the sickle hemoglobin fibers reported in experiments. The process of the cell membrane transition is simulated for physiologic aligned hemoglobin polymer configurations and mean corpuscular hemoglobin concentration. Typical SS-RBC morphologies observed in experiments can be obtained from the current model as a result of the intracellular aligned hemoglobin polymer development without introducing any further ad hoc assumptions. It is found that the final shape of SS-RBCs is primarily determined by the angular width of the aligned hemoglobin polymer domain, but it also depends, to a lesser degree, on the polymer growth rate and the cell membrane rigidity. Cell morphologies are quantified by structural shape factors, which agree well with experimental results from medical images.