title: Direct observation of nanometer-scale pores of melittin in supported lipid monolayers.
abstract: Melittin is the most studied membrane-active peptide and archetype within a large and diverse group of pore formers. However, the molecular characteristics of melittin pores remain largely unknown. Herein, we show by atomic force microscopy (AFM) that lipid monolayers in the presence of melittin are decorated with numerous regularly shaped circular pores that can be distinguished from nonspecific monolayer defects. The specificity of these pores is reinforced through a statistical evaluation of depressions found in Langmuir-Blodgett monolayers in the presence and absence of melittin, which eventually allows characterization of the melittin-induced pores at a quantitative low-resolution level. We observed that the large majority of pores exhibit near-circular symmetry and a Gaussian distribution in size, with a mean diameter of ∼8.7 nm. A distinctive feature is a ring of material found around the pores, made by, on average, three positive peaks, with a height over the level of the lipidic background of ∼0.23 nm. This protruding rim is most likely due to the presence of melittin near the pore border. Although the current resolution of the AFM images in the {x, y} plane does not allow distinction of the specific organization of the peptide molecules, these results provide an unprecedented view of melittin pores formed in lipidic interfaces and open new perspectives for future structural investigations of these and other pore-forming peptides and proteins using supported monolayers.
authors.affiliation: Institute of Molecular Science (ICMol), University of Valencia. C/Catedrático José Beltrán, 2, 46980 Paterna, Valencia, Spain.
authors.forename: Diana
authors.initials: D
authors.lastname: Giménez
authors.affiliation: Institute of Molecular Science (ICMol), University of Valencia. C/Catedrático José Beltrán, 2, 46980 Paterna, Valencia, Spain.
authors.forename: Orlando L
authors.initials: OL
authors.lastname: Sánchez-Muñoz
authors.affiliation: Institute of Molecular Science (ICMol), University of Valencia. C/Catedrático José Beltrán, 2, 46980 Paterna, Valencia, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Salgado
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry; D000595:Amino Acid Sequence; D008055:Lipids / Q000737:chemistry*; D008555:Melitten / Q000737:chemistry* / Q000378:metabolism; D018625:Microscopy, Atomic Force; D008969:Molecular Sequence Data; D036103:Nanotechnology; D016062:Porosity; D011312:Pressure
chemical_list: D008055:Lipids; D008555:Melitten; D015060:1,2-Dipalmitoylphosphatidylcholine