Collaborative Research: Lipid Bilayers and Interfacially Active Peptides

Johns Hopkins University, Baltimore MD

Investigators

Abstract

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 Peptide INTELLECTUAL 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.