Interfacial Phase Behavior of Pulmonary Surfactant

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DESCRIPTION (provided by applicant): This proposal concerns the mechanisms by which thin films of pulmonary surfactant form solid structures in the lungs. Surfactant films stabilize the small air spaces of the lungs by lowering the surface tension of the thin liquid layer that lines the alveoli. When compressed by the decreasing surface area during exhalation, the surfactant film reduces surface tension to extraordinarily low levels. In vitro, compressed monolayers containing the complete set of surfactant constituents fail to reach such low surface tensions because above an equilibrium density, constituents collapse from the interface. The ability of the two dimensional films to flow into the third dimension indicates fluid behavior. In the lungs, the persistence of the surfactant films at the interface when compressed to densities well above equilibrium indicates a solid structure. The classical model of surfactant function contends that only a film in the highly ordered tilted-condensed (TC) phase can be compressed to the low surface tensions observed in the lungs. Of the components in lung surfactant, only its most prevalent constituent, dipalmitoyl phosphatidylcholine (DPPC), can form the TC phase at physiological temperatures. Therefore the classical model explains the transformation of the surfactant film from fluid to solid structures in terms of a change in composition, with elimination of constituents other than DPPC, and a consequent transition between equilibrium phases. Our recently published and preliminary unpublished data, however, disagree with the predictions of the classical model. Our results suggest instead that the fluid surfactant films transform to solid structures by a process analogous to the supercooling of three dimensional liquids to form glass. The experiments proposed here will test first if fluid films transformed to solid structures by supercompression in vitro replicate the behavior of pulmonary surfactant in physiological settings, and then the extent to which the supercompressed fluid monolayers fit predictions of the analogy with supercooled liquids.