Simulated formation of polymer domains in sickle hemoglobin.

Using experimentally observed processes of linear growth, heterogeneous nucleation, and polymer bending, with no additional assumptions, we have been able to model the two-dimensional formation of polymer domains by sickle hemoglobin. The domains begin with twofold symmetry and proceed toward closure into spherulites at a constant rate. Relationships derived from the simulations presented and the requirements of scaling result in simple expressions for the sensitivity of the closure times to the model input parameters and allow the results to be extended to regions not actually simulated. For concentrations above approximately 25 g/dl, closure times are longer than the time required for the conclusion of the polymerization reaction, and thus incomplete spherulites will be the dominant geometry at high concentrations. Moreover, spherulites are not predicted to form in times less than a few seconds, implying that spherulites will not form during the transit of erythrocytes through the capillaries. Polymer-polymer exclusion, surface nucleation, and monomer exhaustion were also explored and found to have only weak effects on the results.