INTERFACIAL PHASE BEHAVIOR OF PULMONARY SURFACTANT

描述(改编自申请人的摘要)：本提案旨在 理解肺表面活性物质界面的结构基础 活动。表面活性物质是脂类和蛋白质的混合物，覆盖在 肺泡，执行稳定凹面空气的基本功能- 液体界面和防止肺泡塌陷在小的肺体积。 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非常高密度的压缩 取决于它的机械特性，而这又是由它的 结构。最近开发的显微方法现在提供了直接访问 到以前可以评估的表面活性剂中的结构相 只是间接的。调查人员使用了荧光显微镜和 布鲁斯特角度显微镜提供了三个初步证据 表面活性剂薄膜压缩过程中的相变顺序： 含大部分DPPC的液体凝聚相的初步分离 剩余的液体膨胀膜；这些相在临界温度下的再混合 点；与紧靠其上的材料形成多层相 和界面单层下方。这些发现表明有重要意义 对传统机构模型的修正 肺表面活性物质在肺中起作用。拟议的研究将测试特定的 关于表面活性剂薄膜中相行为的假设和 这些结构的功能意义。微观方法将会 测定表面活性剂薄膜的相行为和物理性能 不同阶段的特点。其他实验将建立 不同的阶段行为与函数在多大程度上相关 在捕获的气泡上进行体外培养，并在切除的肺中进行原位培养。中的方法 特指强调个体成分的作用，而不仅仅是简单的 模型系统，但也在混合中包含完全复杂的 肺表面活性物质能最大限度地发挥其生理意义 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.