Journal article
The double nucleation model for sickle cell haemoglobin polymerization: Full integration and comparison with experimental data
Acta biotheoretica, v 56(1-2), pp 103-122
01 Jun 2008
PMID: 18247134
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sickle cell haemoglobin (HbS) polymerization reduces erythrocyte deformability, causing deleterous vaso-occlusions. The double-nucleation model states that polymers grow from HbS aggregates, the nuclei, (i) in solution (homogeneous nucleation), (ii) onto existing polymers (heterogeneous nucleation). When linearized at initial HbS concentration, this model predicts early polymerization and its characteristic delay-time (Ferrone et al. J Mol Biol 183(4):591-610, 611-631, 1985). Addressing its relevance for describing complete polymerization, we constructed the full, non-linearized model (Simulink (R), The MathWorks). Here, we compare the simulated outputs to experimental progress curves (n = 6-8 different [HbS], 3-6 mM range, from Ferrone's group). Within 10% from start, average root mean square (rms) deviation between simulated and experimental curves is 0.04 +/- 0.01 (25 degrees C, n = 8; mean +/- standard error). Conversely, for complete progress curves, averaged rms is 0.48 +/- 0.04. This figure is improved to 0.13 +/- 0.01 by adjusting heterogeneous pathway parameters (p < 0.01): the nucleus stability (sigma(2) mu (cc) : + 40%), and the fraction of polymer surface available for nucleation (phi), from 5e(-7), (3 mM) to 13 (6 mM). Similar results are obtained at 37 degrees C. We conclude that the physico-chemical description of heterogeneous nucleation warrants refinements in order to capture the whole HbS polymerization process.
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Details
- Title
- The double nucleation model for sickle cell haemoglobin polymerization: Full integration and comparison with experimental data
- Creators
- Terkia Medkour - Délégation Paris 7Frank Ferrone - Drexel UniversityFrederic Galacteros - Centre de la Drépanocytose et des Thalassémies, CHU Henri Mondor, Creteil, FrancePatrick Hannaert - Inserm
- Publication Details
- Acta biotheoretica, v 56(1-2), pp 103-122
- Publisher
- Springer Nature
- Number of pages
- 20
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000256337900007
- Scopus ID
- 2-s2.0-44949215828
- Other Identifier
- 991019168233004721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Mathematical & Computational Biology