Interfacial Phase Behavior of Pulmonary Surfactant

描述（由申请人提供）：本提案涉及肺表面活性剂薄膜在肺中形成固体结构的机制。表面活性剂薄膜通过降低排列肺泡的薄液体层的表面张力来稳定肺部的小空气空间。当被呼气过程中减少的表面积压缩时，表面活性剂薄膜将表面张力降低到非常低的水平。在体外，含有一整套表面活性剂成分的压缩单层膜无法达到如此低的表面张力，因为在平衡密度以上，成分会从界面崩溃。二维薄膜流入三维的能力表明流体的行为。在肺中，表面活性剂薄膜在被压缩到远高于平衡密度时在界面上的持久性表明是固体结构。表面活性剂功能的经典模型认为，只有高度有序的倾斜凝聚（TC）相的膜才能被压缩到肺部观察到的低表面张力。在肺表面活性剂的成分中，只有其最常见的成分双棕榈酰磷脂酰胆碱（DPPC）能在生理温度下形成TC相。因此，经典模型解释了表面活性剂膜从流体到固体结构的转变，从组成的变化，消除了DPPC以外的成分，以及随之而来的平衡相之间的转变。然而，我们最近发表的和初步未发表的数据与经典模型的预测不一致。我们的研究结果表明，流体表面活性剂薄膜通过类似于三维液体过冷形成玻璃的过程转变为固体结构。本文提出的实验将首先测试通过体外超压缩转化为固体结构的流体膜是否复制生理环境下肺表面活性剂的行为，然后测试超压缩流体单层在多大程度上符合与过冷液体类比的预测。

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 Our recently published and preliminary unpublished data, however, disagree with the predictions of the classical model.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.