STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 肺表面活性物质是肺分泌的脂质和蛋白质的混合物，以覆盖排列在肺泡空气空间中的薄层液体。其功能是降低表面张力，从而防止肺泡在呼气结束时塌陷。两种疏水性表面活性剂蛋白SPB和SP-C，其构成小于1.5%（w/w）的完整混合物，是正常功能所必需的。蛋白质促进表面活性剂囊泡吸附到空气/水界面，使表面活性剂膜在婴儿第一次呼吸时形成初始表面的几秒钟内形成。尽管其重要性，蛋白质促进吸附的机制尚不确定。拟议的研究测试假设，遵循一个模型，其中蛋白质稳定的速率决定，负弯曲的结构，桥梁之间的间隙差距的表面活性剂囊泡和空气/水界面的双层。本实验将确定：（1）分散组分，最初形成单层囊泡（ULV），可以通过小角X射线散射（SAXS）检测，必须转化为多层囊泡（MLV），通过小角X射线衍射（SAXD）测量，以快速吸附;（2）SPs改变了脂质小叶的自发曲率，从SAXD从六边形-II（HII）结构产生的d-间距获得;（3）SP改变了弯曲模量，从有和没有蛋白质的MLV产生的衍射峰的形状获得。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Pulmonary surfactant is the mixture of lipids and proteins that the lungs secrete to coat the thin layer of liquid that lines the alveolar air spaces. Its function is to lower surface tension, thereby preventing alveolar collapse at the end of exhalation. Two hydrophobic surfactant proteins, SPB and SP-C, which constitute less than 1.5% (w/w) of the complete mixture, are essential for normal function. The proteins promote adsorption of surfactant vesicles to the air/water interface, allowing surfactant films to form within seconds of creating the initial surface when a baby takes its first breath. Despite their importance, the mechanisms by which the proteins facilitate adsorption are uncertain. The proposed studies test hypotheses that follow from a model in which the proteins stabilize a rate-determining, negatively curved structure that bridges the gap between the bilayer of a surfactant vesicle and the air/water interface. Our experiments will determine if: (1) dispersed constituents, which initially form unilamellar vesicles (ULV) that can be detected by small angle X-ray scattering (SAXS), must transform to multilamellar vesicles (MLV), measured by small angle X-ray diffraction (SAXD), to adsorb rapidly; (2) the SPs alter the spontaneous curvature of lipid leaflets, obtained from the d-spacing produced by SAXD from hexagonal-II (HII) structures; (3) the SPs alter the bending modulus, obtained from the shape of the diffraction peaks generated by MLV with and without the proteins.