INTERFACIAL ADSORPTION OF PULMONARY SURFACTANT

肺表面活性剂的界面吸附

• 批准号: 6767615
• 负责人: STEPHEN B HALL
• 金额: $ 30.63万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6767615
• 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.

该提案将确定肺表面活性剂吸附到空气-水界面的机制。 表面活性剂是脂质和蛋白质的混合物，覆盖在肺泡内的薄液体层。 表面活性剂薄膜降低了空气-水界面的表面张力，并最大限度地减少了小空气空间的塌陷。 出生时缺乏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。 表面活性剂异常的成年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能会指导开发廉价人工制剂的努力。 为了有效发挥作用，肺表面活性物质必须快速吸附到空气-水界面。 表面活性剂制剂在界面上人工铺展时效果良好，但如果吸收缓慢，则在肺部无效。 我们之前的结果表明，吸附发生在一系列可区分的步骤中，包括最初将囊泡与界面并置，随后将囊泡插入界面，以及吸附的后期加速，在此过程中表面活性剂以某种方式相互作用以产生更快的速率。 我们的数据表明，插入界面是通过囊泡和界面之间的紧密弯曲结构中间发生的，并且吸附的热力学势垒是由紧密弯曲的脂质片层中的酰基链分离引起的不利的焓。 具体目标将检验直接源自该一般模型的假设。 我们将比较不同表面活性剂成分和不同吸附阶段以及囊泡或预先存在的单层中的外在因素对动力学和吸附热力学势垒成分的影响，以确定它们是否通过相同或不同的机制发挥作用。我们将使用布鲁斯特角显微镜监测界面附近未吸附的材料，并使用荧光显微镜跟踪吸附薄膜的成分。