INTERFACIAL PHASE BEHAVIOR OF PULMONARY SURFACTANT

肺表面活性剂的界面相行为

• 批准号: 6185079
• 负责人: STEPHEN B HALL
• 金额: $ 28.22万
• 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 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6185079
• 关键词: animal tissue; chemical stability; cholesterol; compression; fluorescence microscopy; laboratory rat; lipid bilayer membrane; mechanical pressure; palmitates; phosphatidylcholines; pulmonary surfactants; respiratory function

DESCRIPTION (Adapted from the applicant's abstract): This proposal aims to understand the structural basis of pulmonary surfactant's inter-facial activity. Surfactant is the mix of lipids and proteins that coat the alveoli, performing the essential functions of stabilizing the concave air- liquid interface and preventing alveolar collapse at small lung volumes. The ability of surfactant to spread rapidly to form an inter-facial film that can withstand compression during exhalation to very high densities depends upon its mechanical characteristics, which in turn result from its structure. Recently developed microscopic methods now provide direct access to the structural phases in surfactant that previously could be evaluated only indirectly. The investigators have used fluorescence microscopy and Brewster angle microscopy to provide preliminary evidence for three sequential phase transitions during compression of surfactant films: initial separation of a liquid condensed phase containing mostly DPPC from the remaining liquid expanded film; re-mixing of these phases at a critical point; formation of a multi-layered phase with material immediately above and below the inter-facial monolayer. These findings suggest significant modifications of the traditional model for the mechanisms by which surfactant functions in the lung. The proposed studies will test specific hypotheses concerning phase behavior in the surfactant films and the functional significance of these structures. Microscopic methods will determine the phase behavior of surfactant films and the physical characteristics of the different phases. Other experiments will establish the extent to which the different phase behaviors correlate with function in vitro on a captive bubble and in situ in excised lungs. The approach in particular emphasizes the role of individual constituents not just in simple model systems but also in mixtures containing the full complexity of pulmonary surfactant to maximize the physiological significance of the results.

描述（根据申请人的摘要改编）：该提案的目的是 了解肺表面活性剂之间的结构基础 活动。 表面活性剂是脂质和蛋白质的混合物 肺泡，执行稳定凹空气的基本功能 液体界面并防止在小肺体积下肺泡塌陷。 表面活性剂迅速扩散以形成种族间膜的能力 在呼气期间可以承受压缩至非常高的密度 取决于其机械特性，这反过 结构。 最近开发的微观方法现在提供直接访问 表面活性剂中的结构相，以前可以评估 仅间接。 研究人员使用了荧光显微镜和 布鲁斯特角显微镜提供三个初步证据 表面活性剂膜的压缩过程中的顺序相变： 液体冷凝相的初始分离，该相主要包含DPPC 其余的液体膨胀膜；重新混合这些阶段的关键 观点;形成一个多层阶段，材料紧接 并在面间单层下方。 这些发现表明很重要 修改传统模型的机制 表面活性剂在肺中的功能。 拟议的研究将测试特定 关于表面活性剂膜和 这些结构的功能意义。 微观方法将 确定表面活性剂膜的相行为和物理 不同阶段的特征。 其他实验将建立 不同阶段行为与功能中的函数相关的程度 体外在圈养的气泡上，原位在切除的肺中。 方法 特别强调个人成分的作用，不仅在简单中 模型系统，但还包括包含全部复杂性的混合物 肺表面活性剂以最大化生理意义 结果。