INTERFACIAL ADSORPTION OF PULMONARY SURFACTANT

这项申请提出了研究，以建立机制，通过 肺表面活性物质迅速吸附到气液界面形成 能够在压缩过程中降低表面张力的界面膜。 肺表面活性物质使表面张力降至极低水平 在肺中，是正常呼吸所必需的。通过以下方式治疗 早产儿发育前出生的外源性肺表面活性物质 表面活性物质体系使存活率提高了50%。虽然是初步的 结果表明，这种疗法对一些成年人也有效。 疾病，较大剂量的费用禁止考虑其 标准用法。拟议的研究旨在为 通过对机理的理解设计廉价的人工表面活性剂 哪种天然表面活性物质可降低肺表面张力。对土壤的吸附作用 气液界面是表面活性剂活性的关键步骤。最多的 表面活性剂的主要成分二棕榈酰磷脂酰胆碱(DPPC)， 当人工涂布界面膜时，很好地降低了表面张力 压缩的。但DPPC吸附形成这些薄膜的速度非常慢。这 研究试图了解DPPC以外的成分是如何 促进表面活性剂的吸附，形成活性界面膜。这个 实验设计强调包含次要组件，以确保 重要的相互作用不能被忽视。研究考虑了这种影响 表面活性剂的一系列特定组分的吸附 涉及多个步骤的过程。液体中的双层囊泡 相必须在界面上转化为单分子膜，取代任何 预先存在的薄膜，成熟后能够降低表面张力 在压缩过程中。 拟议研究的具体目标是： 1)检验假设表面活性物质的初始吸附速率 对于相对缺乏界面单层的表面，由下式确定 与脂类无关的表面活性蛋白质； 2)测定疏水组分对热释热的影响 气液两相初始吸附的活化熵 界面； 3)检验表面活性物质对An的吸附速率假设 与预先存在的膜的界面取决于存在于 界面单层和亚相囊泡中的蛋白质； 4)检验被吸附的界面膜成熟到 能够在加工前将表面张力降低到低水平的形式 压缩。

This application proposes studies to establish mechanisms by which pulmonary surfactant adsorbs rapidly to an air-liquid interface to form interfacial films capable of reducing surface tension during compression. Pulmonary surfactant reduces surface tension to extraordinarily low levels in the lung and is essential for normal respiration. Treatment with exogenous surfactant of premature infants born prior to the development of the surfactant system has increased survival by 50%. Although preliminary results suggest that this therapy is also effective in some adult disorders, the cost of the larger doses prohibits consideration of its standard use. The proposed research seeks to provide the basis for the design of inexpensive artificial surfactant by understanding mechanisms by which native surfactant lowers surface tension in lung. Adsorption to the air-liquid interface is a critical step in surfactant activity. The most prevalent component of surfactant, dipalmitoyl phosphatidylcholine (DPPC), lowers surface tension well when artificially spread interfacial films are compressed. But DPPC adsorbs to form these films extremely slowly. This research seeks to understand how the constituents other than DPPC facilitate adsorption of surfactant to form active interfacial films. The experimental design emphasizes the inclusion of minor components to ensure that important interactions are not ignored. Studies consider the effect of a range of specific components of surfactant in terms of an adsorption process which involves multiple steps. The bilayer vesicle in the liquid phase must convert to a monomolecular film at the interface, displace any preexisting films, and mature to become capable of lowering surface tension during compression. The specific aims of the proposed research are: 1) to test the hypothesis that the rate of initial surfactant adsorption to a surface relatively devoid of interfacial monolayer is determined by the surfactant proteins, independent of lipids;; 2) to determine the effect of the hydrophobic constituents on the enthalpy and entropy of activation for initial adsorption to the air-liquid interface; 3) to test the hypothesis that the rate of surfactant adsorption to an interface with a preexisting film depends on the lipids present in the interfacial monolayer as well as proteins in the subphase vesicles; 4) to test the hypothesis that the adsorbed interfacial film matures to a form capable of reducing surface tension to low levels prior to undergoing compression.