title: Curvature engineering: positive membrane curvature induced by epsin N-terminal peptide boosts internalization of octaarginine.
abstract: Epsin-1 is a representative protein for inducing the positive curvature necessary for the formation of clathrin-coated pits. Here we demonstrate that the N-terminus 18-residue peptide of epsin-1 (EpN18) has this ability per se, as proved by differential scanning calorimetry (DSC) and solid-state NMR. Moreover, it is shown how this positive curvature promotion can be exploited for promoting the direct penetration of a representative cell-penetrating peptide (CPP), octaarginine (R8), through artificial and plasma membranes. This synergistic effect has been used for the efficient delivery of a proapoptotic domain peptide (PAD), which induced high level of apoptosis only when coadministered with R8 and EpN18, thus emphasizing the importance of positive curvature induction for achieving the desired ultimate cargo bioavailability.
authors.affiliation: Institute for Chemical Research, Kyoto University , Uji, Kyoto 611-0011, Japan.
authors.forename: Sílvia
authors.initials: S
authors.lastname: Pujals
authors.forename: Hiroki
authors.initials: H
authors.lastname: Miyamae
authors.forename: Sergii
authors.initials: S
authors.lastname: Afonin
authors.forename: Tomo
authors.initials: T
authors.lastname: Murayama
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Hirose
authors.forename: Ikuhiko
authors.initials: I
authors.lastname: Nakase
authors.forename: Kentaro
authors.initials: K
authors.lastname: Taniuchi
authors.forename: Masato
authors.initials: M
authors.lastname: Umeda
authors.forename: Kazutami
authors.initials: K
authors.lastname: Sakamoto
authors.forename: Anne S
authors.initials: AS
authors.lastname: Ulrich
authors.forename: Shiroh
authors.initials: S
authors.lastname: Futaki
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000737:chemistry / Q000378:metabolism*; D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D005456:Fluorescent Dyes / Q000008:administration & dosage*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism*; D010455:Peptides / Q000008:administration & dosage*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D057846:Cell-Penetrating Peptides; D004337:Drug Carriers; D005456:Fluorescent Dyes; D009842:Oligopeptides; D010455:Peptides; C114154:epsin; C448619:octaarginine