title: Oligoarginine vectors for intracellular delivery: role of arginine side-chain orientation in chain length-dependent destabilization of lipid membranes.
abstract: Arginine-rich peptides receive increased attention due to their capacity to cross different types of membranes and to transport cargo molecules inside cells. Even though peptide-induced destabilization has been investigated extensively, little is known about the peptide side-chain and backbone orientation with respect to the bilayer that may contribute to a molecular understanding of the peptide-induced membrane perturbations. The main objective of this work is to provide a detailed description of the orientation of arginine peptides in the lipid bilayer of PC and negatively charged PG liposomes using ATR-IR spectroscopy and molecular modeling, and to relate these orientational preferences to lipid bilayer destabilization. Molecular modeling showed that above the transition temperature arginine side-chains are preferentially solvent-directed at the PC/water interface whereas several arginine side-chains are pointing towards the PG hydrophobic core. IR dichroic spectra confirmed the orientation of the arginine side chains perpendicular to the lipid-water interface. IR spectra shows an randomly distributed backbone that seems essential to optimize interactions with the lipid membrane. The observed increase of permeation to a fluorescent dye is related to the peptide induced-formation of gauche bonds in the acyl chains. In the absence of hydrophobic residues, insertion of side-chains that favors phosphate/guanidium interaction is another mechanism of membrane permeabilization that has not been further analyzed so far.
authors: Structure and Function of Biological Membranes, Université Libre de Bruxelles, Boulevard du Triomphe - CP 206/2, B-1050 Brussels, Belgium.
authors: A M
authors: AM
authors: Bouchet
authors: F
authors: F
authors: Lairion
authors: J-M
authors: JM
authors: Ruysschaert
authors: M F
authors: MF
authors: Lensink
mesh_terms: D001120:Arginine / Q000737:chemistry*; D057846:Cell-Penetrating Peptides / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry; D008563:Membrane Lipids / Q000737:chemistry*; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry*; D044367:Phase Transition; D017550:Spectroscopy, Fourier Transform Infrared; D044366:Transition Temperature
chemical_list: D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids; D010455:Peptides; D001120:Arginine