The cell-penetrating peptide TAT(48-60) induces a non-lamellar phase in DMPC membranes.
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 (31)P 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.
Afonin
Sergii
S
Institute of Biological Interfaces, Forschungszentrum Karlsruhe Hermann-von-Helmholtz-Platz 1 76344 Eggenstein-Leopoldshafen, Germany.
Frey
Alexander
A
Bayerl
Sybille
S
Fischer
Dahlia
D
Wadhwani
Parvesh
P
Weinkauf
Sevil
S
Ulrich
Anne S
AS
D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D004134:Dimyristoylphosphatidylcholine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D015696:Gene Products, tat / Q000737:chemistry* / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D017348:Microscopy, Electron, Scanning Transmission; D008954:Models, Biological; D010455:Peptides / Q000737:chemistry*
C108836:1,2-dimyristoyl-sn-glycero-3-ethylphosphocholine; D015696:Gene Products, tat; D008051:Lipid Bilayers; D010455:Peptides; D004134:Dimyristoylphosphatidylcholine