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Supersaturation in sickle cell hemoglobin solutions

J Hofrichter, P D Ross, W A Eaton

    Proceedings of the National Academy of Sciences of the United States of America
    |September 1, 1976
    PubMed
    Summary
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    The gelation of hemoglobin S (HbS) is strongly dependent on its solubility. A new method shows delay time increases significantly with HbS supersaturation, offering insights into sickle cell disease treatment.

    Area of Science:

    • Biophysics
    • Hematology
    • Physical Chemistry

    Background:

    • Sickle cell disease is caused by the polymerization of hemoglobin S (HbS).
    • Understanding the kinetics of HbS gelation is crucial for developing effective treatments.
    • Previous studies have explored factors affecting HbS solubility and gelation.

    Purpose of the Study:

    • To compare the kinetic inhibition of HbS gelation with changes in HbS solubility.
    • To investigate the relationship between HbS supersaturation and gelation delay time.
    • To evaluate the potential of modulating gelation kinetics for therapeutic benefit in sickle cell disease.

    Main Methods:

    • A novel technique was employed to measure both delay time and extent of gelation on the same HbS sample.
    • HbS solubility was altered using carbon monoxide, pH, and urea.

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  • Kinetic data were analyzed using a supersaturation equation.

    • Main Results:

    • The delay time (td) for HbS gelation was found to be proportional to a high power (30-40) of HbS solubility.
    • The rate of gelation is proportional to a high power of supersaturation (S), described by the equation td-1 = gammaSn, with n ≈ 35.
    • The supersaturation equation accurately models the kinetics of HbS gelation.

    Conclusions:

    • HbS gelation kinetics are highly sensitive to supersaturation levels.
    • The developed supersaturation equation provides a quantitative framework for understanding HbS polymerization.
    • Findings suggest that increasing the delay time for sickling could offer clinical benefits for patients with sickle cell disease.