Interfacial Phase Behavior of Pulmonary Surfactant

肺表面活性剂的界面相行为

• 批准号: 6604301
• 负责人: STEPHEN B HALL
• 金额: $ 37万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2006-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6604301
• 关键词: cholesterol; compression; fluorescence microscopy; laboratory rat; lung alveolus; mechanical pressure; palmitates; phosphatidylcholines; phospholipids; pulmonary surfactants; respiratory epithelium; respiratory function

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 Our recently published and preliminary unpublished data, however, disagree with the predictions of the classical model.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

描述（由申请人提供）：该提案涉及肺表面活性剂薄膜在肺中形成固体结构的机制。表面活性剂膜通过降低排列在肺泡上的薄液体层的表面张力来稳定肺部的小空气空间。当在呼气过程中被减小的表面积压缩时，表面活性剂膜将表面张力降低到非常低的水平。在体外，含有全套表面活性剂组分的压缩单层不能达到如此低的表面张力，因为在平衡密度以上，组分从界面塌陷。二维膜流入第三维的能力表明流体行为。在肺中，当被压缩到远高于平衡的密度时，界面处的表面活性剂膜的持久性指示固体结构。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）相的膜可以被压缩到肺中观察到的低表面张力。在肺表面活性物质的组分中，只有其最普遍的组分二棕榈酰磷脂酰胆碱（DPPC）可以在生理温度下形成TC相。因此，经典模型解释了从流体到固体结构的表面活性剂膜在组合物的变化方面的转变，消除了除DPPC以外的成分，以及随之而来的平衡相之间的过渡。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，相反，流体表面活性剂膜转化为固体结构的过程类似于三维液体的过冷形成玻璃。这里提出的实验将首先测试，如果流体膜转化为固体结构的超压缩在体外复制肺表面活性物质在生理环境中的行为，然后在何种程度上的超压缩流体单层适合预测的类比与过冷液体。