Understanding the shape of sickled red cells

¹ NIH

^* To whom correspondence should be addressed. E-mail: eaton{at}helix.nih.gov.

Submitted on August 17, 2004
Revised on September 22, 2004
Accepted on 29 October 2004

	Abstract

To understand the physical basis of the wide variety of shapes of deoxygenated red cells from patients with sickle cell anemia, we have measured the formation rate and volume distribution of the birefringent domains of hemoglobin S fibers. We find that the domain formation rate depends on the ~ 80th power of the protein concentration. This remarkably high concentration dependence, as well as the exponential distribution of domain volumes, can be explained by the previously proposed double nucleation model in which homogeneous nucleation of a single fiber triggers the formation of an entire domain via heterogeneous nucleation and growth. The enormous sensitivity of the domain formation rate to intracellular hemoglobin S concentration explains the variable cell morphology and why rapid polymerization results in cells that do not appear sickled at all.

Key Words: hemoglobin S, nucleation kinetics, polymerization, protein aggregation, protein self assembly, sickle cell disease

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