Rheologic properties of mixed hemoglobin gels: deoxyhemoglobins S and F

To obtain new information concerning the behaviors--and in turn, the structures--of gels formed from mixtures of S and F hemoglobins, their rheologic properties have been characterized by stress relaxation. The variables manipulated were (1) initial total hemoglobin concentration; (2) mole fraction of hemoglobin S present in the mixture; (3) hemoglobin F as only intact tetramer or as both tetramers and hybridized hemoglobin; (4) hemoglobin F as predominantly G gamma, A gamma, or a mixture of gamma chain types; (5) annealing time; (6) shear history, (7) temperature; and (8) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin S and F gels were less solid than pure hemoglobin S gels of similar initial total hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by annealing time, shear history, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin S and F gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. Pathophysiologic implications of these findings for various sickle cell disorders are proposed.