INTERFACIAL ADSORPTION OF PULMONARY SURFACTANT

肺表面活性剂的界面吸附

• 批准号: 6389468
• 负责人: STEPHEN B HALL
• 金额: $ 31万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-05-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6389468
• 关键词: adsorption; biomaterial interface interaction; fluorescence microscopy; lipids; lung alveolus; molecular film; proteins; pulmonary surfactants; surface property; vesicle /vacuole

This proposal will determine the mechanisms by which pulmonary surfactant adsorbs to an air-water interface. Surfactant is the mix of lipids and proteins that coat the thin liquid layer which lines the alveoli. The thin film of surfactant lowers the surface tension of the air-water interface and minimizes collapse of the small air spaces. Premature babies born without adequate levels of surfactant frequently die from respiratory failure unless treated with exogenous surfactant. Adults with abnormal surfactant might also benefit from therapeutic surfactant, but the most effective agents currently are unavailable in sufficient quantities. Understanding the activity of native surfactant may direct efforts to develop inexpensive artificial agents. To function effectively, pulmonary surfactant must adsorb rapidly to the air-water interface. Surfactant preparations that function well when spread artificially at an interface are ineffective in the lung if they adsorb slowly. Our previous results suggest that adsorption occurs in a series of distinguishable steps that include the initial juxtaposition of vesicles to the interface, the subsequent insertion of vesicles into the interface, and a late acceleration of adsorption during which surfactant somehow interacts cooperatively to produce faster rates. Our data suggest that insertion into the interface occurs via a tightly curved structure intermediate between the vesicle and the interface, and that the thermodynamic barrier to adsorption is the unfavorable enthalpy caused by the separation of acyl chains in the tightly bent lipid lamellae. The specific aims will test hypotheses that follow directly from this general model. We will compare the effect of different surfactant components and of extrinsic factors at different stages of adsorption and in the vesicles or in preexisting monolayers on the kinetics and the components of the thermodynamic barrier to adsorption to determine if they function by the same or different mechanisms. We will use Brewster angle microscopy to monitor unadsorbed material adjacent to the interface and fluorescence microscopy to follow the composition of the adsorbed film.

该建议将确定肺表面活性物质吸附到空气-水界面的机制。 表面活性剂是脂质和蛋白质的混合物，覆盖在肺泡的薄层液体上。 表面活性剂薄膜降低了空气-水界面的表面张力，并使小空气空间的塌陷最小化。 出生时没有足够水平的表面活性剂的早产儿经常死于呼吸衰竭，除非用外源性表面活性剂治疗。 患有异常表面活性剂的成人也可能受益于治疗性表面活性剂，但目前最有效的药物数量不足。 了解天然表面活性剂的活性可以指导开发廉价的人工制剂的努力。 为了有效地发挥作用，肺表面活性剂必须迅速吸附到空气-水界面。 表面活性剂制剂在界面处人工扩散时功能良好，但如果它们吸收缓慢，则在肺中无效。 我们以前的研究结果表明，吸附发生在一系列可区分的步骤，包括囊泡的界面，随后插入囊泡到界面的初始并列，和后期加速吸附过程中，表面活性剂以某种方式相互作用，以产生更快的速度。 我们的数据表明，插入到界面发生通过一个紧密弯曲的结构之间的囊泡和界面，和吸附的热力学障碍是不利的焓所造成的分离的酰基链在紧密弯曲的脂质层。 具体目标将检验直接从这一一般模型得出的假设。 我们将比较不同的表面活性剂组分和外在因素在不同阶段的吸附和在囊泡或在预先存在的单分子膜上的动力学和吸附的热力学屏障的组成部分，以确定它们的功能相同或不同的机制。我们将使用布鲁斯特角显微镜监测未吸附的材料相邻的接口和荧光显微镜，以遵循的吸附膜的组成。