title: The efficacies of cell-penetrating peptides in accumulating in large unilamellar vesicles depend on their ability to form inverted micelles.
abstract: In this study, the direct translocation of cell-penetrating peptides (CPPs) into large unilamellar vesicles (LUVs) was shown to be rapid for all the most commonly used CPPs. This translocation led within a few minutes to intravesicular accumulation up to 0.5 mM, with no need for a transbilayer potential. The accumulation of CPPs inside LUVs was found to depend on CPP sequence, CPP extravesicular concentration and phospholipid (PL) composition, either in binary or ternary mixtures of PLs. More interestingly, the role of anionic phospholipid flip-flopping in the translocation process was ascertained. CPPs enhanced the flipping of PLs, and the intravesicular CPP accumulation directly correlated with the amount of anionic PLs that had been transferred from the external to the internal leaflet of the LUV bilayer, thus demonstrating the transport of peptide/lipid complexes as inverted micelles.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, UMR 7203, Laboratoire des Biomolécules; CNRS, UMR 7203, Laboratoire des Biomolécules; ENS, UMR 7203, LBM, Département de Chimie, Ecole Normale Supérieure, 24 Rue Lhomond, 75005 Paris (France).
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Swiecicki
authors.forename: Annika
authors.initials: A
authors.lastname: Bartsch
authors.forename: Julien
authors.initials: J
authors.lastname: Tailhades
authors.forename: Margherita
authors.initials: M
authors.lastname: Di Pisa
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heller
authors.forename: Gérard
authors.initials: G
authors.lastname: Chassaing
authors.forename: Christelle
authors.initials: C
authors.lastname: Mansuy
authors.forename: Fabienne
authors.initials: F
authors.lastname: Burlina
authors.forename: Solange
authors.initials: S
authors.lastname: Lavielle
mesh_terms: D057846:Cell-Penetrating Peptides / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008823:Micelles; D010715:Phosphatidylglycerols / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D008823:Micelles; D010715:Phosphatidylglycerols; D010743:Phospholipids; D053835:Unilamellar Liposomes; C051388:1,2-dioleoyl-sn-glycero-3-phosphoglycerol
keywords: direct translocation; flip-flopping; peptides; phospholipids; vesicles