Supported Lipid Bilayers at the Air-Water Interface: A Comprehensive Mechanistic Study of the Cyclic Peptoid Ml 2-6 on Model Bacteria Membrane Systems

Abstract

In this investigation, three complimentary experimental techniques including atomic force microscopy (AFM), X-ray reflectivity (XR), and epiflourescence microscopy (EFM) were employed to determine the mechanism of action of the antimicrobial cyclic peptoid ML2-6 on model mammalian and bacteria membrane systems. Mammalian and bacterial membranes were mimicked with Langmuir monolayers and supported bilayers both at solid support and at the air-water interface. We introduce a novel approach in which octadecyltrimethoxysilane (OTMS) supported lipid bilayers are used to mimic mammalian and bacterial membranes, which can be probed with X-ray scattering at the air-water interface. ML2-6 was found to be active on all bacteria membrane models, which was deduced by morphological changes observed from AFM and EFM images following the introduction of the peptoid into the system. In addition, XR revealed changes in film thickness and electron-density profile after the addition of ML2-6, consistent with peptoid insertion into phosphatidyl-glycerol (PG) lipid headgroup in both monolayer and bilayer mimics. Conversely, ML2-6 was found to be inactive on all mammalian membrane models investigated, which was concluded form the lack of morphological changes observed from AFM and EFM images when the peptoid was introduced into the system. Furthermore, XR revealed little change in DPPC/Cholesterol film thickness and electron-density profile after the addition of ML2-6. This suggests that ML2-6 may exhibit potential as an antibacterial agent with low cytoxicity to mammalian host cells.