University of Houston associate professor of chemistry, Vassiliy Lubchenko, is reporting a new finding in Nature Communications on how sickle cells are formed. Lubchenko reports that droplets of liquid, enriched in hemoglobin, form clusters inside some red blood cells when two hemoglobin molecules form a bond - but only briefly, for one thousandth of a second or so.
The mystery of how the clusters form has long puzzled scientists. In patients with the inherited blood disorder known as sickle cell disease, or anemia, abnormal hemoglobin molecules line up into stiff filaments inside red blood cells, distorting their shapes and making it difficult for the blood cells to flow through narrow blood vessels. For the filaments to grow, the protein first congregates into tiny liquid droplets that are bigger than an atom, but so small their measurements are counted in increments between microscopic and macroscopic, called mesoscopic.
“Though relatively small in number, the mesoscopic clusters pack a punch,” said Lubchenko. “They serve as essential nucleation, or growth, centers for things like sickle cell anemia fibers or protein crystals. The sickle cell fibers are the cause of a debilitating and painful disease, while making protein crystals remains to this day the most important tool for structural biologists.”
Fibers don’t grow just anywhere. Special, mesoscopically-sized droplets of the protein hemoglobin inside blood cells initiate their formation. “It turns out that inside your blood cell, there are little droplets of hemoglobin that are even more crowded with the protein than the rest of the cell,” said Lubchenko. In an unexpected twist, these crowded areas are also expected to have more molecules bound together into ‘dimers’ or duos, the kind that last only a millisecond.
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Preventing the formation of mesoscopic clusters in blood cells may be one way to prevent sickle cell disease, reports University of Houston associate professor of chemistry Vassiliy Lubchenko. (Photo credit: University of Houston)