Investigations of antimicrobial peptides in planar film systems

Abstract

Planar systems--monolayers and films--constitute a useful platform for studying membrane-active peptides. Here, we summarize varied approaches for studying peptide organization and peptide-lipid interactions at the air/water interface, and focus on three representative antimicrobial membrane--associated peptides-alamethicin, gramicidin, and valinomycin. Experimental data, specifically surface pressure/area isotherms and Brewster angle microscopy images, provided information on peptide association and the effects of the lipid monolayers on peptide surface organization. In general, film analysis emphasized the effects of lipid layers in promoting peptide association and aggregation at the air/water interface. Importantly, the data demonstrated that in many cases peptide domains are phase-separated within the phospholipid monolayers, suggesting that this behavior contributes to the biological actions of membrane-active antimicrobial peptides.

Direct visualization of the alamethicin pore formed in a planar phospholipid matrix

“…This value is in good agreement with the area for Alm molecule oriented with its helical axis parallel to the interface (S state). These results are consistent with the literature which reported that Alm is immiscible with phospholipids in monolayers spread at the air/water interface and the Alm molecules are oriented with axis of the helix parallel to the interface (3,31,32).…”

“…AMPs are biocidally active against Gramnegative and Gram-positive bacteria, fungi, enveloped viruses, eukaryotic parasites, and even tumor cells (3). Importantly, AMPs are effective against strains of antibiotic-resistant bacteria (2).…”

Biomimetic interfaces based on S-layer proteins, lipid membranes and functional biomolecules

“…By far the most literature can be found for the membraneactive peptides alamethicin, valinomycin and gramicidin [166][167][168][169][170][171][172]. The last was also used to determine the fluidity of the lipid membrane and as a molecular force probe [173,174].…”

Biomimetic Model Membrane Systems Serve as Increasingly Valuable in Vitro Tools

“…Most of their AMPs had minimal interaction with zwitterionic lipids, however a few exceptions indicated that electrostatic interactions are not the only attraction between cationic AMPs and negatively charged bacterial membranes. Planar lipid films have also been used combined with Brewster angle microscopy (BAM) to image the interaction of several AMPs with monolayers (Volinski et al, 2006). While two AMPs were immiscible in 1:1 ratios of peptide:DMPC, valinomycin showed phaseseparation in the monolayer.…”

“…Thus, phospholipid-PDA systems could be used, especially in conjunction with BAM, to elucidate surface phenomena of lipid-AMP interactions (Volinski et al, 2006).…”