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Ratchets, red cells, and metastability
Journal article   Open access   Peer reviewed

Ratchets, red cells, and metastability

Frank A Ferrone and Alexey Aprelev
Biophysical reviews, v 5(2), pp 217-224
Jun 2013
DOI: https://doi.org/10.1007/s12551-013-0117-z
PMID: 28510163
url
https://doi.org/10.1007/s12551-013-0117-zView
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Polymerization Molecular crowding Sickle cell disease Brownian ratchet
Sickle cell disease is a genetic disorder in which a negatively charged glutamic acid is replaced by a hydrophobic valine on the surface of the hemoglobin molecule, leading to polymerization of the deoxygenated form, and resulting in microvascular obstruction. Because of the high volume occupancy under which polymerization occurs physiologically, this process has been an exemplar in the study of excluded volume effects on assembly. More recently, we have identified yet another type of crowding effect involving the obstruction of the ends at which the polymers grow as a consequence of the dense arrays in which these polymers form. This makes such solutions metastable, and leads to Brownian ratchet behavior in which pressure is exerted outward when the gel occupies a finite volume, as in an emulsion or red cell. Such behavior is capable of holding sickled cells in place in the microcirculation against weak pressure differentials (hundreds of Pa), but not against the typical pressures found in vivo.

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