Interpretation of the osmotic behavior of sickle cell hemoglobin solutions: different interactions among monomers and...

It has long been known that a simple hard particle model quantitatively explains the osmotic properties of monomeric hemoglobin near its isoelectric point. However, we find that a hard particle model is not consistent with the osmotic properties of polymerized hemoglobin and that substantial soft repulsions are indicated. With allowance for different interactions among monomers and among polymers, a self-consistent quantitative fit to the experimental data is obtained. The results suggest that the decreasing "solubility" of deoxy sickle cell hemoglobin with increasing temperature from 20 to 37 degrees C is due to weaker repulsions between polymers at higher temperatures rather than stronger polymerization. The temperature dependence of these variables indicates that the aggregation of monomers is enthalpically and entropically driven (the latter effect being stronger), while the approach of polymers toward each other is enthalpically disfavored and entropically favored (with the former dominating). In both cases, the entropic contribution suggests that water is released.