LIPID AND PROTEIN EFFECTS ON MONOLAYER STABILITY

开发新的表面活性物质替代品需要(1)了解脂类和蛋白质在天然肺表面活性物质中的作用；(2)开发易于合成的天然表面活性物质蛋白质的类似物；(3)优化脂质组成，以获得低表面张力和快速再铺展和吸附；(4)了解血清蛋白对表面活性物质的抑制作用，并优化表面活性物质的组成，将这种抑制降至最低。我们将使用现代生物物理技术，包括朗缪尔等温线、荧光和布鲁斯特角光学显微镜、原子力显微镜、粘度计和X射线衍射来确定肺表面活性物质的相行为和形态。具体地说：(1)SP-B消除了不饱和脂肪的挤出，使单层塌陷更可逆。SP-C在消除挤出方面效率更高，而在改变崩溃方面效率较低。是否存在SP-B和SP-C的最佳比例，或者这两种蛋白质是否可以互换？(2)我们能制造出更好的SP-B和/或SP-C吗？根据已知的SP-B和SP-C的氨基酸序列，我们将合成一系列模拟SP-B和SP-C特性的同源二聚体多肽。(3)表面活性剂单层膜中是否存在一个最佳的固相分数？向DPPC中添加棕榈酸(PA)会影响流体到固体的相变，并有助于降低表面张力。我们计划测定模型表面活性剂和Survanta中的固相组成。(4)血清蛋白抑制表面活性物质的原因是什么？血液、血浆和血清蛋白、溶菌脂和胎粪可能竞争界面面积，或者可能溶解或降解表面活性物质的成分，从而损害单层功能。我们建议研究模拟肺表面活性物质混合物与人血清白蛋白的相互作用，以确定表面活性物质抑制的分子机制。(S)我们能将单层粘度与单层形态和组成联系起来吗？我们已经建立了磁针粘度计来系统地研究LS单层剪切粘弹性作为以下参数的函数：i)蛋白质含量；ii)单层的相状态。同时，现有的双屏障朗缪尔槽将被改装成在相同条件下进行膨胀粘弹性。

Developing new surfactant substitutes requires (1) understanding the roles of the lipids and proteins in native lung surfactant; (2) developing easy to synthesize analogs of the native surfactant proteins; (3) optimizing lipid composition for low surface tension and rapid respreading and adsorption; (4) understanding surfactant inhibition by serum proteins and optimizing surfactant composition to minimize this inhibition. We will use modern biophysical techniques including Langmuir isotherms, fluorescence and Brewster angle optical microscopy, atomic force microscopy, viscometry, and x-ray diffraction to determine the phase behavior and morphology of lung surfactants. Specifically: (1) SP-B eliminates squeeze-out of unsaturated lipids and makes monolayer collapse more reversible. SP-C is more efficient at eliminating squeeze-out, and is less efficient at altering collapse. Is there an optimal ratio of SP-B to SP-C, or are the proteins interchangable? (2) Can we make a better SP-B and/or SP-C? Based on the known amino acid sequences of SP-B and SP-C, we will synthesize a family of homodimer peptides that mimic the characteristics of SP-B and SP-C. (3) Is there an optimal solid phase fraction in surfactant monolayers? Adding palmitic acid (PA) to DPPC influences the fluid to solid phase transitions and helps lower the surface tension. We plan to determine the composition of the solid phase in model surfactants and Survanta. (4) What leads to surfactant inhibition by serum proteins? Blood, plasma and serum proteins, lysolipids, and meconium may compete for interfacial area or might solubilize or degrade constituents of surfactant, thereby impairing monolayer function. We propose to investigate the interaction of model lung surfactant mixtures with human serum albumin to determine the molecular mechanisms of surfactant inhibition. (S) Can we relate monolayer viscosity to monolayer morphology and composition? We have built a magnetic needle viscometer to carry out systematic studies of LS monolayer shear viscoelasticity as a function of: i) protein content; ii) phase state of the monolayer. Concurrently, an existing double-barrier Langmuir trough will be adapted to do dilational viscoelasticity under the same conditions.