The kinetics of the sol-gel transformation of deoxyhemoglobin S by continuous monitoring of viscosity

Abstract

By continuous monitoring of viscosity during the sol-gel transformation of deoxygenated sickle hemoglobin a time: viscosity profile has been demonstrated that can be subdivided into: (1) initial lag phase, (2) gradual and minor increase in viscosity, (3) rapid and major (180 times initial value) increase in viscosity, (4) moderately rapid decrease in viscosity, and (5) achievement of equilibrium at approximately 50 per cent of maximum viscosity increase. The duration of the lag phase, rate of increase in viscosity, and maximum change are greatly influenced by hemoglobin concentration and markedly altered by temperature. Admixtures of hemoglobins A and F lengthen the lag phase and attenuate the rate of increase and magnitude of viscosity change according to proportions added and capacity to interact with deoxyhemoglobin S, but the general configuration of the curve is maintained. A different time: viscosity profile is obtained for mixtures of S and C hemoglobin that is lacking the phase with decreasing viscosity. Relevance to the pathophysiology of the sickling phenomenon is evidence because the quantitative and qualitative changes induced by variations in concentration of deoxygenated hemoglobin S, temperature, amount and type of admixed hemoglobin (A, C, and F), ionic strength, and 2, 3-DPG are in agreement with their known effects upon the sickling of intact cells and upon the minimum gelling point of deoxyhemoglobin S. No final conclusions can be drawn concerning the extent or form of hemoglobin aggregation present in the various phases of the time: viscosity profile; however, the technique lends itself readily to obtaining samples at various points along the curve for additional studies such as electron microscopy and light scattering.