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Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry
Published on: November 5, 2019
The double nucleation model for sickle cell haemoglobin polymerization: full integration and comparison with
Terkia Medkour1, Frank Ferrone, Frédéric Galactéros
1EA 2381, Pharmacochimie Moléculaire et Systèmes Membranaires, Université Denis Diderot, Paris 7, France.
Acta Biotheoretica
|February 6, 2008
Summary
The double-nucleation model accurately predicts early sickle cell haemoglobin (HbS) polymerization. Refinements to heterogeneous nucleation are needed to fully describe HbS polymerization dynamics.
Area of Science:
- Biophysics
- Hematology
- Computational Biology
Background:
- Sickle cell haemoglobin (HbS) polymerization impairs red blood cell flexibility, leading to vaso-occlusions.
- The double-nucleation model describes HbS polymer growth via homogeneous and heterogeneous nucleation.
- Linearized models predict early polymerization but not complete polymerization dynamics.
Purpose of the Study:
- To construct and validate a full, non-linearized double-nucleation model for HbS polymerization.
- To compare simulation outputs with experimental progress curves.
- To identify necessary refinements in the physico-chemical description of heterogeneous nucleation.
Main Methods:
- Developed a full, non-linearized double-nucleation model using Simulink.
- Compared simulated HbS polymerization curves with experimental data across varying HbS concentrations (3-6 mM) and temperatures (25°C, 37°C).
- Adjusted parameters for nucleus stability and available polymer surface for nucleation to improve model fit.
Main Results:
- The non-linearized model accurately predicted early polymerization (within 10% from start) with low root mean square (rms) deviation (0.04 ± 0.01).
- For complete polymerization curves, the initial model showed higher rms deviation (0.48 ± 0.04).
- Adjusting heterogeneous nucleation parameters significantly improved the model fit for complete curves (rms deviation reduced to 0.13 ± 0.01).
Conclusions:
- The current physico-chemical description of heterogeneous nucleation requires refinement to fully capture HbS polymerization.
- The study highlights the importance of accurate modeling of nucleation processes in understanding sickle cell disease pathophysiology.
- Improved models can aid in developing targeted therapeutic strategies for sickle cell disease.
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