Journal article
Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths
Journal of molecular biology, Vol.315(4), pp.601-612
25 Jan 2002
PMID: 11812133
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Pathogenesis in sickle cell disease depends on polymerization of deoxyhemoglobin S into rod-like fibers, forming gels that rigidify red cells and obstruct the systemic microvasculature. Fiber structure, polymerization kinetics and equilibria are well characterized and intimately related to pathogenesis. However, data on gel rheology, the immediate cause of obstruction, are limited, and models for structure and rheology are lacking. The basis of gel rheology, micromechanics of individual fibers, has never been examined. Here, we isolate fibers by selective depolymerization of gels produced under photolytic deliganding of CO hemoglobin S. Using differential interference contrast (DIC) microscopy, we measure spontaneous, thermal fluctuations in fiber shape to obtain bending moduli (kappa) and persistence lengths (lambda(p)). Some fibers being too stiff to decompose shape accurately into Fourier modes, we measure deviations of fiber midpoints from mean positions. Serial deviations, sufficiently separated to be independent, exhibit Gaussian distributions and provide mean-squared fluctuation amplitudes from which kappa and lambda(p) can be calculated. Lambda(p) ranges from 0.24 to 13 mm for the most flexible and stiffest fibers, respectively. This large range reflects formation of fiber bundles. If the most flexible are single fibers, then lambda(p) =13 mm represents a bundle of seven single fibers. Preliminary data on the bending variations of frozen, hydrated single fibers of HbS obtained by electron microscopy indicate that the value 0.24 mm is consistent with the persistence length of single fibers. Young's modulus is 0.10 GPa, less than for structural proteins but much larger than for extensible proteins. We consider how these results, used with models for cross-linking, may apply to macroscopic rheology of hemoglobin S gels. This new technique, combining isolation of hemoglobin S fibers and measurement of micromechanical properties based on thermal fluctuations and midpoint deviations, can be used to study fibers of mutants, hemoglobin A/S, and mixtures and hybrids of hemoglobin S.
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Details
- Title
- Micromechanics of isolated sickle cell hemoglobin fibers: bending moduli and persistence lengths
- Creators
- Jiang Cheng Wang - Department of Physiology & Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USAMatthew S TurnerGunjan AgarwalSuzanna KwongRobert JosephsFrank A FerroneRobin W Briehl
- Publication Details
- Journal of molecular biology, Vol.315(4), pp.601-612
- Publisher
- England
- Grant note
- HL22654 / NHLBI NIH HHS HL58512 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Identifiers
- 991014878334204721
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- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology