title: Aggregation of oligoarginines at phospholipid membranes: molecular dynamics simulations, time-dependent fluorescence shift, and biomimetic colorimetric assays.
abstract: A time-dependent fluorescence shift method, biomimetic colorimetric assays, and molecular dynamics simulations have been performed in search of explanations why arginine rich peptides with intermediate lengths of about 10 amino acids translocate well through cellular membranes, while analogous lysine rich peptides do not. First, we demonstrate that an important factor for efficient peptide adsorption, as the first prerequisite for translocation across the membrane, is the presence of negatively charged phospholipids in the bilayer. Second, we observe a strong tendency of adsorbed arginine (but not lysine) containing peptides to aggregate at the bilayer surface. We suggest that this aggregation of oligoarginines leads to partial disruption of the bilayer integrity due to the accumulated large positive charge at its surface, which increases membrane-surface interactions due to the increased effective charge of the aggregates. As a result, membrane penetration and translocation of medium length oligoarginines becomes facilitated in comparison to single arginine and very long polyarginines, as well as to lysine containing peptides.
authors.affiliation: Division of Organic Chemistry and Biochemistry, Rudjer Bošković Institute , P.O.B. 180, HR-10002 Zagreb, Croatia.
authors.forename: Mario
authors.initials: M
authors.lastname: Vazdar
authors.forename: Erik
authors.initials: E
authors.lastname: Wernersson
authors.forename: Morteza
authors.initials: M
authors.lastname: Khabiri
authors.forename: Lukasz
authors.initials: L
authors.lastname: Cwiklik
authors.forename: Piotr
authors.initials: P
authors.lastname: Jurkiewicz
authors.forename: Martin
authors.initials: M
authors.lastname: Hof
authors.forename: Ella
authors.initials: E
authors.lastname: Mann
authors.forename: Sofiya
authors.initials: S
authors.lastname: Kolusheva
authors.forename: Raz
authors.initials: R
authors.lastname: Jelinek
authors.forename: Pavel
authors.initials: P
authors.lastname: Jungwirth
mesh_terms: D015081:2-Naphthylamine / Q000031:analogs & derivatives / Q000737:chemistry; D000327:Adsorption; D001120:Arginine / Q000737:chemistry*; D032701:Biomimetics; D003124:Colorimetry; D003911:Dextrans / Q000737:chemistry; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry; D007848:Laurates / Q000737:chemistry; D008051:Lipid Bilayers / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D008564:Membrane Potentials; D056004:Molecular Dynamics Simulation; D009173:Mycophenolic Acid / Q000031:analogs & derivatives / Q000737:chemistry; D010455:Peptides / Q000737:chemistry*; D010713:Phosphatidylcholines / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D010743:Phospholipids / Q000737:chemistry*; D000078789:Polyacetylene Polymer; D011108:Polymers / Q000737:chemistry; D053279:Polyynes / Q000737:chemistry
chemical_list: D003911:Dextrans; D005456:Fluorescent Dyes; D007848:Laurates; D008051:Lipid Bilayers; D010455:Peptides; D010713:Phosphatidylcholines; D010718:Phosphatidylserines; D010743:Phospholipids; D000078789:Polyacetylene Polymer; D011108:Polymers; C050527:dextran T70-mycophenolic acid conjugate; D053279:Polyynes; C015462:polyarginine; C082361:polydiacetylene; C050294:1-palmitoyl-2-oleoylglycero-3-phosphoserine; D001120:Arginine; D015081:2-Naphthylamine; D009173:Mycophenolic Acid; D008239:Lysine; C028694:1-palmitoyl-2-oleoylphosphatidylcholine; C065580:laurdan