title: Membrane selectivity and biophysical studies of the antimicrobial peptide GL13K.
abstract: GL13K is a short (13 amino acid) antimicrobial peptide derived from the parotid secretory protein. GL13K has been found to exhibit anti-inflammatory and antibacterial activities in physiological salt conditions. We investigated the mechanism of interaction of GL13K, with model membranes comprising 1, 2-dioleoylphosphatidylcholine (DOPC) and 1, 2-dioleoylphosphatidylglycerol (DOPG) using various biophysical and imaging techniques. Circular dichroism studies showed that GL13K adopts a β-sheet structure in the presence of negatively charged DOPG liposomes while it retains its random coil structure with zwitterionic DOPC liposomes. GL13K did not cause any fusion of these liposomes but was able to selectively disrupt the negatively charged membranes of DOPG leading to vesicular leakage. There was no or minimal evidence of GL13K interaction with DOPC liposomes, however an analysis of supported lipid bilayers (SLBs) using atomic force microscopic (AFM) imaging and dual polarization interferometry (DPI) suggested that GL13K can interact with the surface of a DOPC planar bilayer. In the case of DOPG bilayers, AFM and DPI clearly showed membrane thinned regions where a portion of lipid molecules has been removed. These results suggest that the mechanism of GL13K action on bacterial membranes involves localized removal of lipid from the membrane via peptide-induced micellization.
authors.affiliation: Department of Chemistry and Biochemistry and the Centre for NanoScience Research, Concordia University, 7141 Sherbrooke St. W., Montreal, Quebec H4B 1R6, Canada.
authors.forename: Vinod
authors.initials: V
authors.lastname: Balhara
authors.forename: Rolf
authors.initials: R
authors.lastname: Schmidt
authors.forename: Sven-Ulrik
authors.initials: SU
authors.lastname: Gorr
authors.forename: Christine
authors.initials: C
authors.lastname: Dewolf
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002942:Circular Dichroism; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010713:Phosphatidylcholines / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol; C017251:1,2-oleoylphosphatidylcholine
keywords: AMPs; Antimicrobial peptide; Antimicrobial peptides; DPI; Dual polarization interferometry; Human parotid secretory protein; Isothermal titration calorimetry; Membrane disruption; Model membrane; P/L; Peptide/lipid ratio; Supported lipid bilayer: atomic force microscopy; TE; TM; Transverse electric phase; Transverse magnetic phase; h-PSP