title: Nanoscale imaging reveals laterally expanding antimicrobial pores in lipid bilayers.
abstract: Antimicrobial peptides are postulated to disrupt microbial phospholipid membranes. The prevailing molecular model is based on the formation of stable or transient pores although the direct observation of the fundamental processes is lacking. By combining rational peptide design with topographical (atomic force microscopy) and chemical (nanoscale secondary ion mass spectrometry) imaging on the same samples, we show that pores formed by antimicrobial peptides in supported lipid bilayers are not necessarily limited to a particular diameter, nor they are transient, but can expand laterally at the nano-to-micrometer scale to the point of complete membrane disintegration. The results offer a mechanistic basis for membrane poration as a generic physicochemical process of cooperative and continuous peptide recruitment in the available phospholipid matrix.
authors.affiliation: National Physical Laboratory, Teddington TW11 0LW, United Kingdom.
authors.forename: Paulina D
authors.initials: PD
authors.lastname: Rakowska
authors.forename: Haibo
authors.initials: H
authors.lastname: Jiang
authors.forename: Santanu
authors.initials: S
authors.lastname: Ray
authors.forename: Alice
authors.initials: A
authors.lastname: Pyne
authors.forename: Baptiste
authors.initials: B
authors.lastname: Lamarre
authors.forename: Matthew
authors.initials: M
authors.lastname: Carr
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Judge
authors.forename: Jascindra
authors.initials: J
authors.lastname: Ravi
authors.forename: Ulla I M
authors.initials: UI
authors.lastname: Gerling
authors.forename: Beate
authors.initials: B
authors.lastname: Koksch
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Martyna
authors.forename: Bart W
authors.initials: BW
authors.lastname: Hoogenboom
authors.forename: Anthony
authors.initials: A
authors.lastname: Watts
authors.forename: Jason
authors.initials: J
authors.lastname: Crain
authors.forename: Chris R M
authors.initials: CR
authors.lastname: Grovenor
authors.forename: Maxim G
authors.initials: MG
authors.lastname: Ryadnov
mesh_terms: D000595:Amino Acid Sequence; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D018625:Microscopy, Atomic Force; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D036103:Nanotechnology / Q000379:methods*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D015202:Protein Engineering; D018629:Spectrometry, Mass, Secondary Ion
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010743:Phospholipids
keywords: antibiotics; de novo protein design; innate host defense; nanometrology; nanoscopy