INTERFACIAL ADSORPTION OF PULMONARY SURFACTANT

这一建议将确定肺表面活性物质吸附到空气-水界面的机制。表面活性物质是脂类和蛋白质的混合物，覆盖在排列在肺泡内的薄薄的液体层上。表面活性剂的薄膜降低了空气-水界面的表面张力，最大限度地减少了小空气空间的坍塌。没有足够水平的表面活性物质出生的早产儿，除非接受外源性表面活性物质治疗，否则往往会死于呼吸衰竭。患有异常表面活性物质的成年人也可能从治疗性表面活性物质中受益，但目前最有效的药物缺乏足够的数量。了解天然表面活性剂的活性可能会指导人们开发廉价的人工试剂。为了有效地发挥作用，肺表面活性物质必须迅速吸附到空气-水界面。如果表面活性物质在界面上人工涂抹时效果良好，如果它们吸附缓慢，则在肺中无效。我们以前的结果表明，吸附发生在一系列可区分的步骤中，包括最初将小泡并列到界面，随后将小泡插入界面，以及后期加速吸附，在此过程中，表面活性剂以某种方式协同作用，产生更快的吸附速率。我们的数据表明，插入到界面上是通过囊泡和界面之间的紧密弯曲结构进行的，吸附的热力学障碍是由于紧密弯曲的脂层中的酰基链分离而产生的不利的热焓。具体的目标将检验直接从这个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吸附不同阶段的外部因素以及在小泡或预先存在的单分子膜中对吸附的动力学和热力学屏障组分的影响，以确定它们的作用机制是相同的还是不同的。我们将使用布鲁斯特角度显微镜来监测界面附近的未吸附物质，并使用荧光显微镜来跟踪被吸附的膜的成分。

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.