STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary surfactant is the mixture of lipids and proteins that the lungs secrete to coat the thin layer of liquid that lines the alveolar air spaces. Its function is to lower surface tension, thereby preventing alveolar collapse at the end of exhalation. Two hydrophobic surfactant proteins, SPB and SP-C, which constitute less than 1.5% (w/w) of the complete mixture, are essential for normal function. The proteins promote adsorption of surfactant vesicles to the air/water interface, allowing surfactant films to form within seconds of creating the initial surface when a baby takes its first breath. Despite their importance, the mechanisms by which the proteins facilitate adsorption are uncertain. The proposed studies test hypotheses that follow from a model in which the proteins stabilize a rate-determining, negatively curved structure that bridges the gap between the bilayer of a surfactant vesicle and the air/water interface. Our experiments will determine if: (1) dispersed constituents, which initially form unilamellar vesicles (ULV) that can be detected by small angle X-ray scattering (SAXS), must transform to multilamellar vesicles (MLV), measured by small angle X-ray diffraction (SAXD), to adsorb rapidly; (2) the SPs alter the spontaneous curvature of lipid leaflets, obtained from the d-spacing produced by SAXD from hexagonal-II (HII) structures; (3) the SPs alter the bending modulus, obtained from the shape of the diffraction peaks generated by MLV with and without the proteins.