Long term objective is to develop a detailed understanding of molecular and structural basis for the theological and adherence properties of sickle red blood cells. Previous studies identify four dominant features: 1) dynamic responses of red cells to folding and extension retarded by dehydration; 2) increased susceptibility to persistent deformations; 3) plasma proteins promote adhesion to endothelial cells; 4) morphologically distinct subsets of red cells are involved in adhesion. Present application proposes to extend these studies to explore the molecular and structural basis for these changes. Specific hypotheses to be tested include: 1. Normal organization and Hb polymerization account for increased membranae rigidity and vulnerability to fragmentation; 2. Thickening of membranes by bound Hv increases dynamic resistance of dense cells to capillary entry; 3. Heterogeneity of rheological properties of dense sickle cells is the result of different mechanisms that lead to dense cell formation; 4. Specific proteins in plasma potentate the anomalous adhesion of sickle cells to endothelial cells; 5. The observed heterogeneity in sickle cell adhesion is due to heterogeneity of expression of specific adhesive receptor(s) on distinct sub populations of sickle cells.
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