STRUCTURAL EFFECTS OF HYDROPHOBIC SURFACTANT PROTEINS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 肺表面活性物质是肺部分泌的脂类和蛋白质的混合物，用来覆盖排列在肺泡空气空间内的薄层液体。其作用是降低表面张力，从而防止呼气末期肺泡塌陷。两种疏水表面活性蛋白SPB和SP-C在整个混合物中所占比例不到1.5%(w/w)，是正常功能所必需的。这些蛋白质促进了表面活性物质小泡在空气/水界面上的吸附，使表面活性物质膜在婴儿第一次呼吸时形成初始表面的几秒钟内就能形成。尽管它们很重要，但蛋白质促进吸附的机制尚不确定。拟议的研究测试了一个模型的假设，在该模型中，蛋白质稳定了一个决定速率的负弯曲结构，该结构弥合了表面活性物质囊泡双层和空气/水界面之间的间隙。我们的实验将确定：(1)分散的成分，最初形成可用小角X射线散射(SAXS)检测的单层小泡(ULV)，是否必须转变为多层小泡(MLV)，用小角X射线衍射(SAXD)测量，以快速吸附；(2)SPS改变脂叶的自发曲率，通过SAXD产生的d间距改变脂叶的自发性曲率；(3)SPS改变由含蛋白质和不含蛋白质的MLV产生的衍射峰的形状获得的弯曲模量。

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.