title: Modulation of lipid membrane structural and mechanical properties by a peptidomimetic derived from reduced amide scaffold.
abstract: Understanding how antimicrobial peptidomimetics interact with lipid membranes is important in battling multidrug resistant bacterial pathogens. We study the effects of a recently reported peptidomimetic on lipid bilayer structural and mechanical properties. The compound referred to as E107-3 is synthesized based on the acylated reduced amide scaffold and has been shown to exhibit good antimicrobial potency. Our vesicle leakage assay indicates that the compound increases lipid bilayer permeability. We use micropipette aspiration to explore the kinetic response of giant unilamellar vesicles (GUVs). Exposure to the compound causes the GUV protrusion length LPto spontaneously increase and then decrease, followed by GUV rupture. Solution atomic force microscopy (AFM) is used to visualize lipid bilayer structural modulation within a nanoscopic regime. Unlike melittin, which produces pore-like structures, the peptidomimetic compound is found to induce nanoscopic heterogeneous structures. Finally, we use AFM-based force spectroscopy to study the impact of the compound on lipid bilayer mechanical properties. We find that incremental addition of the compound to planar lipid bilayers results in a moderate decrease of the bilayer puncture force FPand a 39% decrease of the bilayer area compressibility modulus KA. To explain our experimental data, we propose a membrane interaction model encompassing disruption of lipid chain packing and extraction of lipid molecules. The later action mode is supported by our observation of a double-bilayer structure in the presence of fusogenic calcium ions.
authors.affiliation: Department of Physics, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Nawal K
authors.initials: NK
authors.lastname: Khadka
authors.affiliation: Department of Chemistry, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Peng
authors.initials: P
authors.lastname: Teng
authors.affiliation: Department of Chemistry, University of South Florida, Tampa, FL 33620, United States.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Physics, University of South Florida, Tampa, FL 33620, United States. Electronic address: panj@usf.edu.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Pan
mesh_terms: D000577:Amides / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology; D005452:Fluoresceins / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D057786:Peptidomimetics / Q000494:pharmacology*; D053835:Unilamellar Liposomes / Q000737:chemistry
chemical_list: D000577:Amides; D005452:Fluoresceins; D008051:Lipid Bilayers; D057786:Peptidomimetics; D053835:Unilamellar Liposomes; D002118:Calcium; C007740:fluorexon
keywords: Area compressibility modulus; Atomic force microscopy; Force spectroscopy; Planar lipid bilayer; Puncture force