title: Through the Lipopolysaccharide Glass: A Potent Antimicrobial Peptide Induces Phase Changes in Membranes.
abstract: In the following, molecular simulations are used to reveal unexpected behavior within bacterial membranes. We show that lipopolysaccharide molecules found in these membranes form viscous amorphous solids when they are interlinked with monovalent and divalent cations. The bilayers exhibit both liquid and glassy characteristics, due to the coexistence of both liquid and crystalline domains in the bilayer. Polymyxin B1, a potent antimicrobial peptide, is shown to increase order within the lipopolysaccharide bilayers by inducing the formation of crystalline patches. Crucially we are able to decompose the energetics of insertion into their enthalpic and entropic components. The present coarse-grain molecular dynamics study provides unprecedented insights into the antibacterial action of antimicrobial peptides, thus paving the way for development of novel therapeutic agents to treat multiple drug resistant Gram-negative bacteria.
authors.affiliation: School of Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
authors.forename: Damien
authors.initials: D
authors.lastname: Jefferies
authors.affiliation: School of Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
authors.forename: Pin-Chia
authors.initials: PC
authors.lastname: Hsu
authors.affiliation: School of Chemistry, University of Southampton , Southampton, SO17 1BJ, U.K.
authors.forename: Syma
authors.identifier: 0000-0002-3694-5044
authors.initials: S
authors.lastname: Khalid
mesh_terms: D002118:Calcium / Q000737:chemistry*; D002413:Cations, Divalent; D002414:Cations, Monovalent; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D003460:Crystallization; D006090:Gram-Negative Bacteria / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008070:Lipopolysaccharides / Q000737:chemistry*; D056004:Molecular Dynamics Simulation; D044367:Phase Transition / Q000187:drug effects; D011113:Polymyxins / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D012964:Sodium / Q000737:chemistry*; D013816:Thermodynamics
chemical_list: D002413:Cations, Divalent; D002414:Cations, Monovalent; D008051:Lipid Bilayers; D008070:Lipopolysaccharides; D011113:Polymyxins; D012964:Sodium; C121746:polymyxin B(1); D002118:Calcium