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Characterization of Sickling During Controlled Automated Deoxygenation with Oxygen Gradient Ektacytometry
Published on: November 5, 2019
Electrochemical modulation of sickle cell haemoglobin polymerisation
Zeshan Iqbal1, Rachel McKendry, Michael Horton
1Department of Chemistry, University College London, 20 Gordon St., London, WC1 H 0AJ, UK.
The Analyst
|December 21, 2006
Summary
Researchers developed an electrochemical method to study sickle cell haemoglobin (HbS) polymerization. This technique monitors HbS fiber formation, crucial for developing new sickle cell disease treatments.
Area of Science:
- Biochemistry
- Materials Science
- Electrochemistry
Background:
- Sickle cell haemoglobin (HbS) polymerization into insoluble fibers causes disease pathology.
- Polymerization is triggered by low oxygen levels, leading to protein conformational changes.
Purpose of the Study:
- To develop an electrochemical method for controlling oxygen levels and monitoring HbS polymerization.
- To investigate the kinetics of HbS fibrillogenesis, specifically nucleation and elongation phases.
Main Methods:
- An electrochemical method was used to modulate oxygen concentration in an optically transparent thin layer cell.
- Turbidity measurements were employed to monitor the extent of HbS polymerization.
- A two-step fibrillogenesis model (nucleation and elongation) was used to analyze polymerization kinetics.
Main Results:
- Nucleation was found to be significantly slower than elongation in HbS polymerization.
- Nucleation rate constants were dependent on monomer concentration, while growth rate constants were largely independent.
- Rate constants for nucleation and growth were determined at different HbS monomer concentrations.
Conclusions:
- The developed electrochemical method provides a novel approach for studying HbS polymerization.
- This methodology can serve as a screening tool for identifying potential therapeutic agents targeting HbS fiber formation.
- Understanding nucleation and growth kinetics is vital for developing effective sickle cell disease treatments.
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