INTEGRATION OF FTIR AND A CAPTIVE BUBBLE SURFACTOMETER

目前的方法，无论是从仪器灵敏度还是设计上，都不能有效地研究肺表面活性剂蛋白的结构和/或功能。确定这些蛋白的功能机制对NRDS和ARDS治疗的发展至关重要。这将通过将灵敏的红外光谱技术（ATR-FTIR）与独特的俘获泡表面计（CBS）相结合来实现，从而产生一种能够精确模拟生理条件的制剂的脂质/蛋白质相互作用和表面活性剂蛋白质结构的方法。本研究的目标是优化CBS/ATR-FTIR采样室中FTIR光谱采集的参数，优化CBS组件表面张力测量的参数和仪器，并集成CBS/ATR-FTIR采样附件的所有组件，以完成计算机化的仪器控制和数据采集。这种配置将允许同时测量1)单层表面压力，2)蛋白质结构（作为表面压力的函数），3)蛋白质和脂质取向（相对于表面压力），以及4)表面活性剂蛋白质和其他蛋白质（例如膜受体，抗菌肽）在脂质单层界面上的蛋白质/脂质相互作用。通过CBS/ATR-FTIR同时测量结构/功能，可以描绘出健康和患病肺中每种表面活性物质蛋白在肺表面活性物质生物学功能中的作用。在不久的将来，对更复杂的表面活性剂蛋白质/脂质混合物的实验可能有助于改善和发展婴儿、儿童和成人表面活性剂缺乏性疾病的治疗方法。

Current methods, whether from instrumental sensitivity or design, have not been capable of effectively studying the structure and/or function of pulmonary surfactant proteins. It is crucial for the development of treatments for NRDS and ARDS that the mechanisms by which these proteins function be determined. This will be accomplished by combining a sensitive infrared spectroscopic technique (ATR-FTIR) with a unique captive bubble surfactometer (CBS) to yield a method that will be capable of defining lipid/protein interactions and surfactant protein structure of preparations that accurately mimic physiological conditions. The goals of the proposed research are to optimize parameters for FTIR spectral acquisition in the CBS/ATR-FTIR sample chamber, to optimize parameters and instrumentation for surface tension measurements by the CBS component, and to integrate all components of the CBS/ATR-FTIR sampling accessory for complete computerized instrumental control and data acquisition. This configuration will permit simultaneous measurement of 1) monolayer surface pressure, 2) protein structure (as a function of surface pressure), 3) protein and lipid orientation (vs. surface pressure), and 4) protein/lipid interactions of surfactant proteins and other proteins (e.g., membrane receptors, antimicrobial peptides) at a lipid monolayer interface. Simultaneous structure/function measurements by CBS/ATR-FTIR will make it possible to delineate the role of each surfactant protein in the biological function of pulmonary surfactant in healthy and diseased lungs. In the near future, experiments with more complex surfactant protein/lipid mixtures may aid in the improvement and development of treatments for surfactant deficient diseases in infants, children and adults.