Mathematical Model Yields Clues to Sickle Cell Disease

Researchers have developed a mathematical model of sickle cell disease in an effort to understand why the mutant hemoglobin proteins form long, stable scaffold-like structures that damage red blood cells rather than less harmful compact crystals.

The mutated form of hemoglobin in individuals with sickle cell disease does not remain in solution in the cytoplasm. Instead, it tends to coagulate into long fibers. A sickle hemoglobin fiber can be made up of anywhere from 14 to more than 400 individual strands of hemoglobin molecules linked into long chains.

Researchers at the University of Warwick (UK) constructed the mathematical molecule to explain the stability of these fibers. The model, which was published March 28, 2003, in the online edition of Physical Review Letters, indicated that an inherent "twistiness” in the strands that comprise the fibers could be the key to their durability.

The authors proposed a possible treatment for sickle cell disease based on their model. Gene therapy might be used to introduce a hemoglobin mutant that would form less-twisty individual strands, and this could turn the fibers into less harmful crystals. Simply introducing normal hemoglobin has been shown not to work, perhaps because the few normal hemoglobin molecules cannot eliminate the fibers.



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