title: Interaction of the Antimicrobial Peptides Rhesus θ-Defensin and Porcine Protegrin-1 with Anionic Phospholipid Monolayers.
abstract: A combination of Langmuir isotherm, Brewster angle microscopy (BAM), and neutron reflectivity studies have been performed to gain insight into the effects on model bacterial cell membranes of the antimicrobial peptides, Rhesus θ-defensin 1 (RTD-1), and porcine protegrin 1 (PG-1). The peptides were interacted with monolayers spread at the air-water interface and prepared from a 3:1 molar mixture of phosphatidylethanolamine and phosphatidylglycerol used to approximate the cell membranes of Gram positive bacteria. The Langmuir film balance measurements show that both peptides perturb the lipid monolayers causing an increase in surface pressure, and the BAM studies show that each results in the formation of small domains within the lipid films, around 5 μm diameter. The overall change in monolayer surface pressure caused by PG-1, however, is a little more pronounced than that due to RTD-1 (+8.5 mN·m(-1) vs +5.5 mN·m(-1)), and the rate of its initial interaction with the monolayer is a little more rapid than that for RTD-1. The neutron reflectivity studies also show differences for PG-1 and RTD-1, with the model fits to these data showing that the more amphiphilic PG-1 becomes fully embedded within the lipid film-causing an extension of the lipid acyl chains but leaving the thickness of the lipid headgroup layer unaffected-while RTD-1 is seen to insert less deeply-causing the same extension of the lipid acyl chains as PG-1 but also causing a significant increase in thickness of the lipid headgroup layer. The various differing effects of the two peptides on anionic lipid monolayers are discussed in the context of their differing hemolytic activities, and their proposed differing propensities to form transmembrane pores.
authors.affiliation: Institute of Pharmaceutical Science, King's College London , London SE1 9NH, United Kingdom.
authors.forename: Ivana
authors.initials: I
authors.lastname: Knyght
authors.affiliation: Rutherford Appleton Laboratory, ISIS Spallation Neutron Source, Harwell OX11 0QX, United Kingdom.
authors.forename: Luke
authors.initials: L
authors.lastname: Clifton
authors.affiliation: Institute of Pharmaceutical Science, King's College London , London SE1 9NH, United Kingdom.
authors.forename: Yussif
authors.initials: Y
authors.lastname: Saaka
authors.affiliation: Institute of Pharmaceutical Science, King's College London , London SE1 9NH, United Kingdom.
authors.forename: M Jayne
authors.initials: MJ
authors.lastname: Lawrence
authors.affiliation: Institute of Pharmaceutical Science, King's College London , London SE1 9NH, United Kingdom.
authors.forename: David J
authors.initials: DJ
authors.lastname: Barlow
mesh_terms: D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D008253:Macaca mulatta; D008567:Membranes, Artificial; D008958:Models, Molecular; D010743:Phospholipids / Q000737:chemistry*; D013552:Swine; D023084:alpha-Defensins / Q000737:chemistry*
chemical_list: D023181:Antimicrobial Cationic Peptides; D008567:Membranes, Artificial; D010743:Phospholipids; D023084:alpha-Defensins; C094880:protegrin-1