Interfacial Phase Behavior of Pulmonary Surfactant

肺表面活性剂的界面相行为

基本信息

批准号：
6779061
负责人：
STEPHEN B HALL
金额：
$ 36.74万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
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

项目摘要

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 Our recently published and preliminary unpublished data, however, disagree with the predictions of the classical model.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肺泡内薄液体层的表面张力来稳定肺部的小空气空间。当呼气过程中表面积减小而受到压缩时，表面活性剂膜将表面张力降低到极低的水平。在体外，含有全套表面活性剂成分的压缩单层无法达到如此低的表面张力，因为高于平衡密度，成分从界面塌陷。二维薄膜流入三维的能力表明了流体行为。在肺中，当压缩至远高于平衡的密度时，表面活性剂膜在界面处的持久性表明存在固体结构。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）相的薄膜才能被压缩到在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，经典模型通过成分的变化解释了表面活性剂膜从流体到固体结构的转变，消除了除 DPPC 以外的成分，以及随之而来的平衡相之间的转变。然而，我们最近发布的和初步未发布的数据与经典模型的预测不一致。我们的结果表明，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。这里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中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的类比预测。