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Rapid and inefficient kinetics of sickle hemoglobin fiber growth
In sickle cell disease, the aberrant assembly of hemoglobin fibers induces changes in red blood cell morphology and stiffness, which leads to downstream symptoms of the disease. Therefore, understanding of this assembly process will be important for the treatment of sickle cell disease. By performin...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2019
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415962/ https://www.ncbi.nlm.nih.gov/pubmed/30891490 http://dx.doi.org/10.1126/sciadv.aau1086 |
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author | Castle, Brian T. Odde, David J. Wood, David K. |
author_facet | Castle, Brian T. Odde, David J. Wood, David K. |
author_sort | Castle, Brian T. |
collection | PubMed |
description | In sickle cell disease, the aberrant assembly of hemoglobin fibers induces changes in red blood cell morphology and stiffness, which leads to downstream symptoms of the disease. Therefore, understanding of this assembly process will be important for the treatment of sickle cell disease. By performing the highest spatiotemporal resolution measurements (55 nm at 1 Hz) of single sickle hemoglobin fiber assembly to date and combining them with a model that accounts for the multistranded structure of the fibers, we show that the rates of sickle hemoglobin addition and loss have been underestimated in the literature by at least an order of magnitude. These results reveal that the sickle hemoglobin self-assembly process is very rapid and inefficient (4% efficient versus 96% efficient based on previous analyses), where net growth is the small difference between over a million addition-loss events occurring every second. |
format | Online Article Text |
id | pubmed-6415962 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-64159622019-03-19 Rapid and inefficient kinetics of sickle hemoglobin fiber growth Castle, Brian T. Odde, David J. Wood, David K. Sci Adv Research Articles In sickle cell disease, the aberrant assembly of hemoglobin fibers induces changes in red blood cell morphology and stiffness, which leads to downstream symptoms of the disease. Therefore, understanding of this assembly process will be important for the treatment of sickle cell disease. By performing the highest spatiotemporal resolution measurements (55 nm at 1 Hz) of single sickle hemoglobin fiber assembly to date and combining them with a model that accounts for the multistranded structure of the fibers, we show that the rates of sickle hemoglobin addition and loss have been underestimated in the literature by at least an order of magnitude. These results reveal that the sickle hemoglobin self-assembly process is very rapid and inefficient (4% efficient versus 96% efficient based on previous analyses), where net growth is the small difference between over a million addition-loss events occurring every second. American Association for the Advancement of Science 2019-03-13 /pmc/articles/PMC6415962/ /pubmed/30891490 http://dx.doi.org/10.1126/sciadv.aau1086 Text en Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). http://creativecommons.org/licenses/by-nc/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial license (http://creativecommons.org/licenses/by-nc/4.0/) , which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited. |
spellingShingle | Research Articles Castle, Brian T. Odde, David J. Wood, David K. Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title | Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title_full | Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title_fullStr | Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title_full_unstemmed | Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title_short | Rapid and inefficient kinetics of sickle hemoglobin fiber growth |
title_sort | rapid and inefficient kinetics of sickle hemoglobin fiber growth |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6415962/ https://www.ncbi.nlm.nih.gov/pubmed/30891490 http://dx.doi.org/10.1126/sciadv.aau1086 |
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