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Interfacial Phase Behavior of Pulmonary Surfactant

肺表面活性剂的界面相行为

基本信息

批准号：
8097367
负责人：
STEPHEN B HALL
金额：
$ 38.5万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1998
资助国家：
美国
起止时间：
1998-08-01 至 2014-06-30
项目状态：
已结题

项目摘要

DESCRIPTION (provided by applicant): This proposal seeks to define the mechanisms by which films of pulmonary surfactant become capable of sustaining low surface tensions in the lungs. Adsorption of surfactant vesicles lowers surface tension from 70 mN/m for a clean air/water interface to ~25 mN/m, but multiple methods show that alveolar surface tensions reach values <5 mN/m. These lower values occur in dynamic lungs when the decreasing alveolar surface area during exhalation compresses the adsorbed films. To reach these low surface tensions, the films must avoid collapse of the film from the interface by flow into a three dimensional bulk phase. Two monomolecular films related to pulmonary surfactant can mimic the ability of the surfactant films to reach and sustain the very low surface tensions that occur in the alveolus. Dipalmitoyl phosphatidylcholine (DPPC), which is the most prevalent components of surfactant from most species, forms a highly ordered interfacial phase at physiological temperatures that resists collapse during compression and reaches very low surface tension. Disordered films containing either individual phospholipids or the complete set of surfactant constituents also become capable of sustaining very low surface tensions if compressed fast enough to outrun collapse and reach these low surface tensions. Although both the DPPC and supercompressed films can mimic the behavior of the alveolar film, mechanisms by which either structure could form are unknown. Processes that could produce the change in composition from an initial film containing all surfactant constituents to one that includes only DPPC is unclear. The supercompressed films also seem to require compressions faster than are necessary in the lungs for the films to reach low surface tensions. The proposed studies, which are largely based on these two films, consider specific mechanisms by which physiological processes could generate either film. The experiments test specific hypotheses concerning how the films become capable of sustaining low surface tensions. Our methods emphasize specific structural and functional changes predicted by different models, and specific dependence on composition. The models follow directly from results obtained during previous periods of this grant, and the experiments rely on methods established during those studies. The experiments should address a fundamental unanswered question of pulmonary physiology that has direct implications for the mechanisms of disease and for the development of new therapies. PUBLIC HEALTH RELEVANCE: Pulmonary surfactant forms films that coat the surface of a thin liquid layer that lines the small air sacks of the lungs, and minimizes their tendency to deflate. The mechanisms by which the surfactant films become exceptionally stable, and particularly able to prevent collapse of the air spaces, are unknown. The proposed studies seek to determine these mechanisms as a basis for understanding how pulmonary surfactant functions in the lungs, and how artificial therapeutic surfactants might be designed for the treatment of pulmonary diseases.

描述(由申请人提供)：本提案旨在定义肺表面活性物质膜能够维持肺内低表面张力的机制。表面活性物质泡的吸附将表面张力从清洁空气/水界面的70mN/m降低到~25mN/m，但多种方法表明，肺泡表面张力达到&lt；5mN/m。当呼气过程中肺泡表面积减小压缩被吸附的膜时，这些较低的值出现在动态肺中。为了达到这些低表面张力，薄膜必须避免薄膜通过流动进入三维主体相而从界面坍塌。两个与肺表面活性物质相关的单分子膜可以模拟表面活性物质膜达到并维持肺泡内非常低的表面张力的能力。Dipalmitoyl磷脂酰胆碱(DPPC)是大多数物种中最常见的表面活性剂成分，它在生理温度下形成高度有序的界面相，在压缩过程中抵抗坍塌，并达到非常低的表面张力。含有单个磷脂或整套表面活性剂成分的无序薄膜也能够维持非常低的表面张力，如果压缩得足够快，以超过崩溃并达到这些低表面张力的话。虽然DPPC和超压缩膜都可以模仿牙槽膜的行为，但这两种结构形成的机制尚不清楚。从含有所有表面活性剂成分的初始膜到只含有DPPC的膜的组成变化的过程尚不清楚。超压缩薄膜似乎也需要比肺部达到低表面张力所需的压缩速度更快。拟议中的研究主要基于这两种膜，考虑了生理过程产生这两种膜的具体机制。这些实验测试了关于薄膜如何能够维持低表面张力的具体假设。我们的方法强调不同模型预测的特定结构和功能变化，以及对成分的特定依赖。这些模型直接遵循在这笔赠款的前几个时期获得的结果，而实验依赖于在那些研究期间建立的方法。这些实验应该解决一个对疾病机制和新疗法的开发有直接影响的基本的肺生理学问题。与公共健康相关：肺表面活性物质形成薄膜，覆盖在肺部小气囊的薄薄液体层的表面，并将其放气的倾向降至最低。表面活性剂薄膜变得异常稳定，特别是能够防止空气空间坍塌的机制尚不清楚。拟议的研究试图确定这些机制，作为了解肺表面活性物质如何在肺中发挥作用的基础，以及如何设计人工治疗性表面活性物质来治疗肺部疾病。

项目成果

期刊论文数量（20）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Transformation diagrams for the collapse of a phospholipid monolayer.

磷脂单层塌陷的转化图。

DOI：
10.1021/la049081t
发表时间：
2004
期刊：
Langmuir : the ACS journal of surfaces and colloids
影响因子：
0
作者：
Rugonyi,Sandra;Smith,EthanC;Hall,StephenB
通讯作者：
Hall,StephenB

Liquid-crystalline collapse of pulmonary surfactant monolayers.

肺表面活性剂单层的液晶塌陷。

DOI：
10.1016/s0006-3495(03)75107-8
发表时间：
2003
期刊：
Biophysical journal
影响因子：
3.4
作者：
Schief,WilliamR;Antia,Meher;Discher,BohdanaM;Hall,StephenB;Vogel,Viola
通讯作者：
Vogel,Viola

The collapse of monolayers containing pulmonary surfactant phospholipids is kinetically determined.

含有肺表面活性剂磷脂的单层的塌陷是由动力学决定的。

DOI：
10.1529/biophysj.105.060947
发表时间：
2005
期刊：
Biophysical journal
影响因子：
3.4
作者：
Yan,Wenfei;Piknova,Barbora;Hall,StephenB
通讯作者：
Hall,StephenB

Location of the Hydrophobic Surfactant Proteins, SP-B and SP-C, in Fluid-Phase Bilayers.

DOI：
10.1021/acs.jpcb.0c03665
发表时间：
2020-08-06
期刊：
The journal of physical chemistry. B
影响因子：
0
作者：
Loney RW;Panzuela S;Chen J;Yang Z;Fritz JR;Dell Z;Corradi V;Kumar K;Tieleman DP;Hall SB;Tristram-Nagle SA
通讯作者：
Tristram-Nagle SA

The melting of pulmonary surfactant monolayers.

肺表面活性剂单层的熔化。