Journal article
Universal Metastability of Sickle Hemoglobin Polymerization
Journal of molecular biology, v 377(4), pp 1228-1235
04 Apr 2008
PMID: 18308336
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sickle hemoglobin (HbS) polymerization occurs when the concentration of deoxyHbS exceeds a well-defined solubility. In experiments using sickle hemoglobin droplets suspended in oil, it has been shown that when polymerization ceases the monomer concentration is above equilibrium solubility. We find that the final concentration in uniform bulk solutions (i.e., with negligible boundaries) agrees with the droplet measurements, and both exceed the expected solubility. To measure hemoglobin in uniform solutions, we used modulated excitation of trace amounts of CO in gels of HbS. In this method, a small amount of CO is introduced to a spatially uniform deoxyHb sample, so that less than 2% of the sample is liganded. The liganded fraction is photolyzed repeatedly and the rate of recombination allows the concentration of deoxyHbS in the solution phase to be determined, even if polymers have formed. Both uniform and droplet samples exhibit the same quantitative behavior, exceeding solubility by an amount that depends on the initial concentration of the sample, as well as conditions under which the gel was formed. We hypothesize that the early termination of polymerization is due to the obstruction in polymer growth, which is consistent with the observation that pressing on slides lowers the final monomer concentration, making it closer to solubility. The thermodynamic solubility in free solution is thus achieved only in conditions with low polymer density or under external forces (such as found in sedimentation) that disrupt polymers. Since we find that only about 67% of the expected polymer mass forms, this result will impact any analysis predicated on predicting the polymer fraction in a given experiment.
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Details
- Title
- Universal Metastability of Sickle Hemoglobin Polymerization
- Creators
- Weijun Weng - Department of Physics, Drexel University, Philadelphia, PA 19104, USAAlexey Aprelev - Department of Physics, Drexel University, Philadelphia, PA 19104, USARobin W Briehl - Department of Physiology and Biophysics, and Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461, USAFrank A Ferrone - Department of Physics, Drexel University, Philadelphia, PA 19104, USA
- Publication Details
- Journal of molecular biology, v 377(4), pp 1228-1235
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000255108900020
- Scopus ID
- 2-s2.0-40849114308
- Other Identifier
- 991014878144004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology