INTEGRATION OF FTIR AND A CAPTIVE BUBBLE SURFACTOMETER

目前的方法，无论是从仪器的灵敏度或设计，还没有能够有效地研究肺表面活性蛋白的结构和/或功能。 确定这些蛋白的作用机制对于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）与独特的捕获气泡表面活性仪（CBS）相结合来实现，以产生一种能够定义脂质/蛋白质相互作用和精确模拟生理条件的制剂的表面活性剂蛋白质结构的方法。 建议的研究的目标是优化参数的FTIR光谱采集在CBS/ATR-FTIR样品室，优化参数和仪器的表面张力测量的CBS组件，并整合所有组件的CBS/ATR-FTIR采样配件，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），和4）表面活性剂蛋白质和其它蛋白质（例如，膜受体、抗微生物肽）。 CBS/ATR-FTIR的结构/功能同时测量将有可能描绘每个表面活性物质蛋白在肺表面活性物质在健康和患病肺的生物学功能中的作用。 在不久的将来，用更复杂的表面活性剂蛋白/脂质混合物进行的实验可能有助于改善和开发婴儿、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.