Pulmonary surfactant is defective in the neonatal Respiratory Distress Syndrome (RDS) of premature infants and in the acute RDS (ARDS) that occurs in patients of all ages. Rapid adsorption of surfactant vesicles to form a thin film at the air-water interface in the lungs is essential both for the function of native surfactant and for the efficacy of any exogenous therapeutic surfactant. The small hydrophobic surfactant proteins greatly facilitate the process of adsorption by mechanisms that remain unknown. Studies on the analogous fusion between bilayer membranes suggest that the process occurs at defects in the lipid packing at the boundary between two phases within the membrane. The proposed studies will investigate the model that surfactant adsorption also occurs at lipid defects, and that the surfactant proteins promote adsorption by extending the length of the interfacial boundary in surfactant vesicles.
The specific aims will test the hypotheses that the length of boundary correlates with the rate of adsorption using vesicles containing binary mixtures of phospholipids, and that the surfactant proteins extend the boundary between phases in phospholipid vesicles.
