This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Poly(phenylene ethyneylene) (PPE)-based cationic conjugated polyelectrolytes (CPE) and cationic phenylene ethynylene oligomers (OPE) exhibit broad-spectrum antimicrobial activity and one of their main target is believed to be the cell membrane. To better understand the biocidal mechanism of these antimicrobial molecules, it is important to gain a fundamental understanding of the interactions of CPEs/OPEs with model lipid membranes. A series of PPE-based CPE and OPE with different size and functional groups are planed to be tested. Small/Large unilamellar vesicles with lipid compositions mimicking those of mammalian or bacterial membranes will be used as model membranes. The state-of-the-art synchrotron small-angle x-ray scattering technology at SSRL is planed to be used to detect the location of these antimicrobial compounds in the lipid bilayer and study the topological transition of the model membrane induced by the CPEs/OPEs. Based on the literatures, if the membrane-active antimicrobial agents could create membrane defects or transmembrane pores, compared with the pure model membranes, it would be possible to observe new x-ray diffraction peaks from the mixture of the model membrane and the antimicrobial compound in SAXS experiments. We plan to use SAXS to study CPEs/OPEs induced topological transition and phase separation of model lipid membranes. The upcoming results of this study will provide solid evidence for CPEs/OPEs-lipid interactions and help to better understand the antimicrobial mechanism of the CPEs and OPEs. Meanwhile, the outcomes may provide guidelines to developing more efficient and selective antimicrobial agents.
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