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.

journal_name

Chem Phys Lipids

authors

Bouchet AM,Lairion F,Ruysschaert JM,Lensink MF

doi

10.1016/j.chemphyslip.2011.11.008

subject

Has Abstract

pub_date

2012-01-01 00:00:00

pages

89-96

issue

1

eissn

0009-3084

issn

1873-2941

pii

S0009-3084(11)00355-0

journal_volume

165

pub_type

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