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The Cell-Penetrating Peptide TAT(48-60) Induces a Non-Lamellar Phase in DMPC Membranes

Authors

  • Sergii Afonin Dr.,

    1. Institute of Biological Interfaces, Forschungszentrum Karlsruhe Hermann-von-Helmholtz-Platz 1 76344 Eggenstein-Leopoldshafen, Germany, Fax: (+49) 721-608-4823,
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  • Alexander Frey,

    1. Institute of Organic Chemistry, Universität Karlsruhe (TH) Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
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  • Sybille Bayerl Dr.,

    1. Department of Chemistry, Technische Universität München Lichtenbergstr. 4, 85747 Garching, Germany
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  • Dahlia Fischer Dr.,

    1. Institute of Organic Chemistry, Universität Karlsruhe (TH) Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
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  • Parvesh Wadhwani Dr.,

    1. Institute of Biological Interfaces, Forschungszentrum Karlsruhe Hermann-von-Helmholtz-Platz 1 76344 Eggenstein-Leopoldshafen, Germany, Fax: (+49) 721-608-4823,
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  • Sevil Weinkauf Prof. Dr.,

    1. Department of Chemistry, Technische Universität München Lichtenbergstr. 4, 85747 Garching, Germany
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  • Anne S. Ulrich Prof. Dr.

    1. Institute of Biological Interfaces, Forschungszentrum Karlsruhe Hermann-von-Helmholtz-Platz 1 76344 Eggenstein-Leopoldshafen, Germany, Fax: (+49) 721-608-4823,
    2. Institute of Organic Chemistry, Universität Karlsruhe (TH) Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
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Abstract

Cell-penetrating peptides (CPPs) are short polycationic sequences that can translocate into cells without disintegrating the plasma membrane. CPPs are useful tools for delivering cargo, but their molecular mechanism of crossing the lipid bilayer remains unclear. Here we study the interaction of the HIV-derived CPP TAT (48-60) with model membranes by solid-state NMR spectroscopy and electron microscopy. The peptide induces a pronounced isotropic 31P NMR signal in zwitterionic DMPC, but not in anionic DMPG bilayers. Octaarginine and to a lesser extent octalysine have the same effect, in contrast to other cationic amphiphilic membrane-active peptides. The observed non-lamellar lipid morphology is attributed to specific interactions of polycationic peptides with phosphocholine head groups, rather than to electrostatic interactions. Freeze-fracture electron microscopy indicates that TAT(48-60) induces the formation of rodlike, presumably inverted micelles in DMPC, which may represent intermediates during the translocation across eukaryotic membranes.

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