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（改编自申请人的摘要）：该提案旨在 了解肺表面活性物质界面的结构基础 活动。 表面活性剂是脂质和蛋白质的混合物，覆盖在 肺泡，执行稳定凹面空气的基本功能 液体界面并防止小肺容量时的肺泡塌陷。 表面活性剂快速铺展形成界面膜的能力 可以在呼气时承受压缩到非常高的密度 取决于其机械特性，而机械特性又源于其 结构。 最近开发的显微方法现在可以直接访问 以前可以评估的表面活性剂的结构相 只是间接的。 研究人员使用荧光显微镜 布鲁斯特角显微镜为三者提供初步证据 表面活性剂薄膜压缩过程中的连续相变： 主要含有 DPPC 的液体凝聚相的初步分离 剩余的液体膨胀膜；在临界点重新混合这些相 观点;与紧邻其上方的材料形成多层相 和低于界面单层。 这些发现表明意义重大 对传统机制模型的修改 表面活性剂在肺中发挥作用。 拟议的研究将测试具体 关于表面活性剂膜中的相行为的假设和 这些结构的功能意义。 显微方法将 确定表面活性剂膜的相行为和物理 不同阶段的特点。 其他实验将建立 不同相行为与功能的相关程度 在体外的圈养气泡上和在切除的肺部原位进行。 该方法在 特别强调个体成分的作用，而不仅仅是简单的 模型系统，但也包含包含全部复杂性的混合物 肺表面活性物质最大限度地发挥其生理意义 结果。