INTERFACIAL PHASE BEHAVIOR OF PULMONARY SURFACTANT

描述（改编自申请人摘要）：本提案旨在 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， 肺泡，执行稳定凹空气的基本功能- 液体界面和防止肺泡塌陷在小肺体积。 表面活性剂迅速扩散形成界面膜的能力 在呼气过程中可以承受很高密度的压缩 取决于其机械特性，而机械特性又是由其 结构 最近开发的显微镜方法现在提供了直接进入 表面活性剂中的结构相，以前可以评估 只是间接的。 研究人员使用荧光显微镜， 布鲁斯特角显微镜提供了三个初步证据 表面活性剂膜压缩过程中的连续相变： 将主要含有DPPC的液体冷凝相与 剩余的液体膨胀膜;在临界温度下重新混合这些相， 点;形成多层相，其上紧接着有材料 和低于界面单层。 这些发现表明， 对传统机制模型的修改， 表面活性剂在肺中起作用。 拟议的研究将测试具体的 关于表面活性剂膜中相行为的假设， 这些结构的功能意义。 显微镜方法将 确定表面活性剂膜的相行为和物理性质 不同阶段的特点。 其他实验将建立 不同的相行为与功能相关的程度， 在捕获气泡上的体外和在切除的肺中的原位。 中的方法 特别强调的作用，个别成分不只是在简单的 模型系统，但也在混合物包含完整的复杂性， 肺表面活性物质，以最大限度地发挥生理意义的 结果

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.