Intellectual Merit: Artificial bacterial cell membranes are to be chemically assembled on patterned gold surfaces. Protein diffusion and the resulting membrane structures will be evaluated to verify that the laboratory platform mimics properties of cell membranes. The fabricated membranes will then serve as a test platform to study pore formation due to interactions between bactericidal proteins and membrane surfaces. Pore formation will be measured by an ion current that results across the membrane when a pore is formed. The toxicity of antimicrobial proteins will be determined by cell-based cytotoxicity assays and related to electrochemical properties. Patterning of membranes structures in array format will be also be developed for high-throughput studies of protein-membrane interactions.
Broader Impacts: This project involves the fabrication of a laboratory platform for use in the identification of the next generation of antibiotics in response to increasing bacterial resistance to current antibiotics. Pore formation due to assembly of proteins on cell surfaces that occurs under natural circumstances is a mechanism for killing bacterial cells while leaving mammalian cells intact. The development of artificial cell membrane arrays will allow for rapid screening of potential bactericidal agents as well as studies of drug delivery mechanisms across cell membranes. Both graduate and undergraduate students will perform research to gain advanced analytical training in interdisciplinary research. The research activities and results will also be used as case studies in the investigators' undergraduate courses in order to educate a larger pool of students in interdisciplinary research.
