Journal article
The Effects of Erythrocyte Membranes on the Nucleation of Sickle Hemoglobin
Biophysical journal, v 88(4), pp 2815-2822
2005
PMID: 15653736
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Pathology in sickle cell disease begins with nucleation-dependent polymerization of deoxyhemoglobin S into stiff, rodlike fibers that deform and rigidify red cells. We have measured the effect of erythrocyte membranes on the rate of homogeneous nucleation in sickle hemoglobin, using preparations of open ghosts (OGs) with intact cytoskeletons from sickle (SS) and normal adult (AA) red cells. Nucleation rates were measured by inducing polymerization by laser photolysis of carboxy sickle hemoglobin and observing stochastic variation of replicate experiments of the time for the scattering signals to reach 10% of their respective maxima. By optical imaging of membrane fragments added to a hemoglobin solution we contrast the rate of nucleation immediately adjacent to membrane fragments with nucleation in a region of the same solution but devoid of membranes. From analysis of 29,272 kinetic curves obtained, we conclude that the effect of AA OGs is negligible (10% enhancement of nucleation rates ±20%), whereas SS OGs caused 80% enhancement (±20%). In red cells, where more membrane surface is available to Hb, this implies enhancement of nucleation by a factor of 6. These experiments represent a 10-fold improvement in precision over previous approaches and are the first direct, quantitative measure of the impact of erythrocyte membranes on the homogeneous nucleation process that is responsible for polymer initiation in sickle cell disease.
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Details
- Title
- The Effects of Erythrocyte Membranes on the Nucleation of Sickle Hemoglobin
- Creators
- Alexey Aprelev - Department of Physics, Drexel University, Philadelphia, PennsylvaniaMaria A Rotter - Department of Physics, Drexel University, Philadelphia, PennsylvaniaZipora Etzion - Department of Medicine, Albert Einstein College of Medicine, Bronx, New YorkRobert M Bookchin - Department of Medicine, Albert Einstein College of Medicine, Bronx, New YorkRobin W Briehl - Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, New YorkFrank A Ferrone - Department of Physics, Drexel University, Philadelphia, Pennsylvania
- Publication Details
- Biophysical journal, v 88(4), pp 2815-2822
- Publisher
- Elsevier
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Physics
- Web of Science ID
- WOS:000227986300040
- Scopus ID
- 2-s2.0-22144455299
- Other Identifier
- 991014878136304721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biophysics