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Dissertation
Heterogeneous nucleation of sickle hemoglobin: structural modeling and experimental evidence
Doctor of Philosophy (Ph.D.), Drexel University
1999
DOI:
https://doi.org/10.17918/00008028
Abstract
Sickle Hemoglobin molecules assemble into polymers composed of seven helically twisted double strands. Intermolecular contacts within the double strands are well established. We show that the same contact sites are present at the polymer surface on four molecules in each layer, and demonstrate that the identical contact geometry can be achieved between fibers. This provides a structural rationale for the exponential polymer growth that characterizes the kinetics of gelation. This also gives a structural basis for the cross-linking which solidifies the gel. The thermodynamical characteristics of polymerization are elucidated by the double nucleation model, which assumes two ways of polymerization-homogeneous and heterogeneous. Introducing the predictions from our structural model into the theoretical description of the double nucleation model, we develop a new way of data analysis for calculation of the heterogeneous nucleation rate, the size of the nucleus, and the heterogeneous nucleation sites availability. This is verified against results from Sickle Hemoglobin experiments. Having the theoretical tools, we test the viability of our model experimentally. Since the mutation is on both [beta]-chains of the Sickle Hemoglobin tetramer, replacement of one of them with normal [beta]-chain will reduce the number of polymerization sites but not inhibit gelation. We measure the nucleation rates of Hemoglobin with one normal and one mutant [beta]-chain, cross-linked for stability. The results show twofold increase of the nucleus size, 10³-10⁴ times smaller homogeneous nucleation rate, 10²-10³ times smaller heterogeneous nucleation rate, and significant decrease with strong temperature dependence of the heterogeneous nucleation site availability which varies 14 orders of magnitude over a 10°C temperature range.
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Details
- Title
- Heterogeneous nucleation of sickle hemoglobin
- Creators
- Rossen Mirchev
- Contributors
- Frank Ferrone (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- xii, 94 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Arts and Sciences; Drexel University
- Other Identifier
- 991021889103704721