title: Antimicrobial peptide dendrimer interacts with phosphocholine membranes in a fluidity dependent manner: A neutron reflection study combined with molecular dynamics simulations.
abstract: The interaction mechanism of a novel amphiphilic antimicrobial peptide dendrimer, BALY, with model lipid bilayers was explored through a combination of neutron reflection and molecular dynamics simulations. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1,2-dipalmitoyl-sn-glycero-3-phos-phocholine (DPPC) lipid bilayers were examined at room temperature to extract information on the interaction of BALY with fluid and gel phases, respectively. Furthermore, a 1:4 mixture of POPC and DPPC was used as a model of a phase-separated membrane. Upon interaction with fluid membranes, BALY inserted in the distal leaflet and caused thinning and disordering of the headgroups. Membrane thinning and expansion of the lipid cross-sectional area were observed for gel phase membranes, also with limited insertion to the distal leaflet. However, dendrimer insertion through the entire lipid tail region was observed upon crossing the lipid phase transition temperature of DPPC and in phase separated membranes. The results show clear differences in the interaction mechanism of the dendrimer depending on the lipid membrane fluidity, and suggest a role for lipid phase separation in promoting its antimicrobial activity.
authors.affiliation: Institute of Chemistry and Nano-Science Center, University of Copenhagen, Universitetsparken 5, DK 2100 Copenhagen, Denmark; European Spallation Source ESS AB, P.O. Box 176, 22100 Lund, Sweden.
authors.forename: T K
authors.initials: TK
authors.lastname: Lind
authors.affiliation: Department of Chemistry, King's College London, London SE1 9NH, UK.
authors.forename: L
authors.initials: L
authors.lastname: Darré
authors.affiliation: Department of Chemistry, King's College London, London SE1 9NH, UK; Chemistry Research Laboratory, Mansfield Road, University of Oxford, Oxford OX1 3TA, UK.
authors.forename: C
authors.initials: C
authors.lastname: Domene
authors.affiliation: Institute of Organic Chemistry, Polish Academy of Sciences, 01-224 Warsaw, Poland.
authors.forename: Z
authors.initials: Z
authors.lastname: Urbanczyk-Lipkowska
authors.affiliation: Institute of Chemistry and Nano-Science Center, University of Copenhagen, Universitetsparken 5, DK 2100 Copenhagen, Denmark; Malmoe University, Health & Society, 20506 Malmoe, Sweden. Electronic address: marite.cardenas@mah.se.
authors.forename: M
authors.initials: M
authors.lastname: Cárdenas
authors.affiliation: Institute of Chemistry and Nano-Science Center, University of Copenhagen, Universitetsparken 5, DK 2100 Copenhagen, Denmark; European Spallation Source ESS AB, P.O. Box 176, 22100 Lund, Sweden. Electronic address: hanna.wacklin@esss.se.
authors.forename: H P
authors.initials: HP
authors.lastname: Wacklin
mesh_terms: D015060:1,2-Dipalmitoylphosphatidylcholine / Q000737:chemistry*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D003198:Computer Simulation; D050091:Dendrimers; D008051:Lipid Bilayers / Q000737:chemistry*; D008560:Membrane Fluidity; D008956:Models, Chemical; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D033363:Neutron Diffraction / Q000379:methods; D010713:Phosphatidylcholines / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D050091:Dendrimers; D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D015060:1,2-Dipalmitoylphosphatidylcholine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine
keywords: Antimicrobial interactions; Dendrimer; Lipid bilayers; Molecular dynamics simulations; Neutron reflection