Collaborative Research: Lipid Bilayers and Interfacially Active Peptides

ID：MPS/DMR/BMAT（7623）1003441 PI：Hristova，Kalina 组织机构：约翰霍普金斯大学ID：MPS/DMR/BMAT（7623）1003411 PI：Wimley，William ORG：杜兰大学标题：合作研究：脂质双层和界面活性肽智力优势：界面活性肽结合到双层膜和驱动脂质重排。 这种界面活性有两种不同的结果，要么（1）双层不稳定导致溶质通过膜泄漏，要么（2）肽易位而没有显著的溶质泄漏。 然而，目前尚不清楚是哪些因素决定了这两种截然不同的结果。 由于仍然缺乏对机制的理解，目前还不可能预测特定肽如何与脂质双层相互作用。 在这个提议中，PI从三个家族中选择了19种肽：界面活性肽，易位肽和膜非活性肽。 这些肽家族已经使用13，000种肽的高通量正交筛选来鉴定。 所选择的肽将根据其与双层的结合、在双层中的布置以及对双层电性质的影响来表征。 具体而言，PI将使用中子反射率和衍射表征脂质双层中三个家族（泄漏诱导，易位和非活性）的肽的处置。 在第二条攻击线中，他们将使用电化学阻抗谱（EIS）表征支持的双层对三个肽家族（泄漏诱导，易位和非活性）的电响应。这些实验将在已知的结合肽浓度的指导下进行初步工作的结果。更广泛的影响：科学更广泛的影响在于这个项目的能力，以确定界面活性肽的化学结构和它们的作用模式之间的相关性。 了解这些相关性将允许设计新的肽，可能有治疗或科学应用。 该项目将赞助杜兰大学和约翰霍普金斯大学之间的学生交流。 特别是，计划由杜兰大学的一名研究生对约翰霍普金斯大学进行为期六个月的访问，并由新奥尔良高中学生和杜兰大学本科生进行夏季访问。 其目的是向新奥尔良的学生介绍材料科学作为一门学科，因为新奥尔良大学没有材料科学系。 这两个机构的实验室将包括研究团队的本科生，以保持长期的实践。 约翰霍普金斯集团将与JHU妇女科学和工程项目合作，接触巴尔的摩地区的女高中生，努力使她们对科学和工程职业感兴趣。

ID: MPS/DMR/BMAT(7623) 1003441 PI: Hristova, Kalina ORG: Johns Hopkins University ID: MPS/DMR/BMAT(7623) 1003411 PI: Wimley, William ORG: Tulane University Title: Collaborative Research: Lipid Bilayers and Interfacially Active PeptideINTELLECTUAL MERIT: Interfacially active peptides bind to bilayer membranes and drive the rearrangement of lipids. There are two different outcomes of this interfacial activity, either (1) bilayer destabilization leading to leakage of solutes through the membrane, or (2) peptide translocation without significant solute leakage. However, it is not known which factors determine these two very different outcomes. Because a mechanistic understanding is still lacking, it is not currently possible to predict how a particular peptide will interact with a lipid bilayer. In this proposal, the PIs have selected 19 peptides from within three families: interfacially active peptides, translocating peptides, and membrane inactive peptides. These peptide families have been identified using a high throughput, orthogonal screen of 13,000 peptides. The selected peptides will be characterized in terms of their binding to bilayers, disposition in bilayers, and effects on bilayer electrical properties. Specifically, the PIs will characterize the disposition of peptides from the three families (leakage-inducing, translocating, and inactive) in lipid bilayers using neutron reflectivity and diffraction. In a second line of attack they will characterize the electrical response of supported bilayers to the three families of peptides (leakage-inducing, translocating, and inactive) using electrochemical impedance spectroscopy (EIS). These experiments will be performed at known bound peptide concentrations guided by the outcome of preliminary work.BROADER IMPACTS: The scientific broader impacts lie in the capacity of this project to identify correlations between the chemical structure of interfacially active peptides and their mode of action. Understanding of these correlations will then permit design of new peptides that may have therapeutic or scientific applications. The project will sponsor student exchanges between Tulane and Johns Hopkins. In particular, a six month visit to Johns Hopkins by a graduate student from Tulane and summer visits by New Orleans high school students and Tulane undergraduates are planned. The intention is to introduce the students from New Orleans to materials science as a discipline, given that there are no materials science departments at the New Orleans universities. The laboratories at both institutions will include undergraduates on the research teams in keeping with long standing practice. The Johns Hopkins group will collaborate with the JHU Women in Science and Engineering program to reach out to female high school students in the Baltimore area in an effort to interest them in careers in science and engineering.