The aims of the total program are to investigate the rheological behavior of human red blood cell (RBC) and white blood cell (WBC) membranes to study the interactions of these membranes with their environment, to correlate membrane functions with molecular organization, and to evaluate the role of blood cell properties in circulatory regulation, in health and disease. Rheology of normal and abnormal RBC and WBC is studied by biomechanical techniques, microviscosity measurement, ultrastructural methods and theoretical computation. Rheological data are correlated with the molecular organization of membrane, especially membrane proteins and protein-lipid interactions. The multidisciplinary approach is used to study: changes in membrane rheology during deoxygenation of sickle cells; the relation of I-i antigens on cell exoface to intracellular Hb F; properties of hexose receptor transport protein; electrochemical forces involved in interactions of RBC exoface with macromolecules; and the micromechanics of cell aggregation. The role of blood cell properties in affecting flow dynamics and metabolic transport is studied in the macro- and microcirculation. The above projects are supported by core facilities in the ultrastructure laboratory, hematology clinic, instrumentation laboratory and computer unit where additional funds are requested for equipment essential to the research in various projects. This supplemental application is submitted mainly for the renewal of the project on Force Balance in Cell Interactions, with emphasis on the elucidation of physicochemical factors affecting cell agglutination by antibodies and lectins. This project constitutes an essential component of our coordinated effort with the ultimate goal of providing the fundamental knowledge needed to improve diagnosis and treatment of cardiovascular and blood diseases.