Metastable Polymerization of Sickle Hemoglobin in Droplets

Alexey Aprelev, Weijun Weng, Mikhail Zakharov, Maria Rotter, Donna Yosmanovich, Suzanna Kwong, Robin W. Briehl, Frank A. Ferrone

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Sickle cell disease arises from a genetic mutation of one amino acid in each of the two hemoglobin β chains, leading to the polymerization of hemoglobin in the red cell upon deoxygenation, and is characterized by vascular crises and tissue damage due to the obstruction of small vessels by sickled cells. It has been an untested assumption that, in red cells that sickle, the growing polymer mass would consume monomers until the thermodynamically well-described monomer solubility was reached. By photolysing droplets of sickle hemoglobin suspended in oil we find that polymerization does not exhaust the available store of monomers, but stops prematurely, leaving the solutions in a supersaturated, metastable state typically 20% above solubility at 37 °C, though the particular values depend on the details of the experiment. We propose that polymer growth stops because the growing ends reach the droplet edge, whereas new polymer formation is thwarted by long nucleation times, since the concentration of hemoglobin is lowered by depletion of monomers into the polymers that have formed. This finding suggests a new aspect to the pathophysiology of sickle cell disease; namely, that cells deoxygenated in the microcirculation are not merely undeformable, but will actively wedge themselves tightly against the walls of the microvasculature by a ratchet-like mechanism driven by the supersaturated solution.

Original languageEnglish (US)
Pages (from-to)1170-1174
Number of pages5
JournalJournal of Molecular Biology
Volume369
Issue number5
DOIs
StatePublished - Jun 22 2007

Keywords

  • Brownian ratchet
  • self-assembly
  • solubility
  • vasooccclusion

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Aprelev, A., Weng, W., Zakharov, M., Rotter, M., Yosmanovich, D., Kwong, S., Briehl, R. W., & Ferrone, F. A. (2007). Metastable Polymerization of Sickle Hemoglobin in Droplets. Journal of Molecular Biology, 369(5), 1170-1174. https://doi.org/10.1016/j.jmb.2007.04.030