The goal of the project is to establish the motor mechanism utilized by blood cells involved in defense of the host against infection to move, ingest foreign matter and secrete inflammatory mediators. An understanding of this mechanism may permit physicians in the future to modify these functions and thereby improve host defense, diminish inflammation, and inhibit the movement and division of malignant blood cells. It is known that the region of blood cells responsible for these functions is the peripheral cytoplasm. Accordingly, the research concerns an analysis of the molecules which comprise cortical cytoplasm, principally actin and actin-associated proteins. The proposed project plans to study the stucture and function of individual components, specifically actin-binding protein, which is responsible for the branching of actin fibers, myosin, responsible for contractile events, and two other proteins, alphaactinin and tropomyosin, proteins whose functions in the blood cell are unknown. The project will also examine quantitatively the ultrastructure and rheology of actin assemblies prepared with purified actin-associated proteins. In addition, the ultrastructure of cortical cytoplasmic actin fibers in detergent extracted blood cells will be examined and the location of actin-associated proteins determined by immunocytochemistry. The intention is to correlate the ultrastructure of cortical cytoplasm with that of actin assemblies prepared in vitro with purified actin-associated proteins at concentrations which exist in the cell. Taken together with the rheologic data on purified proteins, it should be possible to estimate the mechanical properties of peripheral cytoplasm. Finally, the estimates will be tested by direct measurements of cellular mechanics.
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