Erythrocyte membrane mechanics
Abstract
The erythrocyte membrane provides a fundamental model from which the molecular organization of more complex cells may be elucidated. Traditionally, two major erythrocyte bridges are believed to maintain structural integrity and elastic flexibility of the cell: band 3 - ankyrin - β-spectrin and glycophorin C - protein 4.1 - β-spectrin. However, although evidence substantiates the constitutive role of the first bridge, disrupting or breaking the glycophorin C - protein 4.1 bridge does not appear to weaken membrane stability. Here we reveal the presence of an additional third bridge via a novel band 3 - β-adducin interaction that is critical for maintaining normal membrane morphology. Unlike the other two bridges, this new bridge directly links the junctional complex to the anion exchanger and, once characterized, will increase knowledge of both band 3 and adducin roles in the erythrocyte and may provide insight into certain blood disorders. Additionally, we provide the first evidence that a secreted cytokine, osteopontin, directly influences red blood cell rheology. Osteopontin decreases red blood cell filterability and induces cytosolic calcium efflux in erythroid progenitor cells, mature murine red blood cells, and mature human red blood cells. Osteopontin also recuperates the detrimental effects of A23187, a calcium ionophore, which induces cell shrinkage, membrane vesiculation, and hemolysis. Recent investigations also give evidence that osteopontin, similar to its restorative effects of A23187-damaged erythrocytes, acts to recondition sickle cells to intrinsic biconcave morphologies.
Degree
Ph.D.
Advisors
Low, Purdue University.
Subject Area
Biochemistry
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