IFLYSIB   05383
INSTITUTO DE FISICA DE LIQUIDOS Y SISTEMAS BIOLOGICOS
Unidad Ejecutora - UE
artículos
Título:
Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell penetrating peptides
Autor/es:
HENRY DAVID HERCE; ANGEL ENRIQUE GARCIA; JEFF LITT; RAVI KANE; PEDRO MARTIN; NICOLAS ENRIQUE; ALEJANDRO REBOLLEDO; VERONICA MILESI
Revista:
BIOPHYSICAL JOURNAL
Editorial:
CELL PRESS
Referencias:
Año: 2009 vol. 97 p. 1917 - 1925
ISSN:
0006-3495
Resumen:
Recent molecular dynamics simulations (Herce and Garcia, PNAS, 104: 20805 (2007)) have suggested that the arginine-rich HIV Tat peptides might be able to translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, arginine residues play a fundamental role not only in the binding of the peptide to the surface of the membrane but also in the destabilization and nucleation of transient pores across the bilayer, despite being charged and highly hydrophilic. Here we present a molecular dynamics simulation of a peptide composed of nine arginines (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test this hypothesis experimentally by measuring ionic currents across phospholipid bilayers and cell membranes through the pores induced by Arg-9 peptides. We find that Arg-9 peptides, in the presence of an electrostatic potential gradient, induce ionic currents across planar phospholipid bilayers, as well as in cultured osteosarcoma cells and human smooth muscle cells freshly isolated from the umbilical artery. Our results suggest that the mechanism of action of Arg-9 peptide involves the creation of transient pores in lipid bilayers and cell membranes.