Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides

Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg residues play a fundamental role not only in the binding of the peptide to t...

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Detalles Bibliográficos
Autores principales: Herce, H. D., Garcia, A. E., Litt, J., Kane, R. S., Martín, Pedro, Enrique, Nicolás Jorge, Rebolledo, Alejandro, Milesi, Verónica
Formato: Articulo
Lenguaje:Inglés
Publicado: 2009
Materias:
Ciencias Exactas
Args
peptides
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/82765
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-82765
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Ciencias Exactas
Args
peptides
spellingShingle Ciencias Exactas
Args
peptides
Herce, H. D.
Garcia, A. E.
Litt, J.
Kane, R. S.
Martín, Pedro
Enrique, Nicolás Jorge
Rebolledo, Alejandro
Milesi, Verónica
Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
topic_facet Ciencias Exactas
Args
peptides
description Recent molecular-dynamics simulations have suggested that the arginine-rich HIV Tat peptides translocate by destabilizing and inducing transient pores in phospholipid bilayers. In this pathway for peptide translocation, Arg 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. Here we present a molecular-dynamics simulation of a peptide composed of nine Args (Arg-9) that shows that this peptide follows the same translocation pathway previously found for the Tat peptide. We test experimentally the hypothesis that transient pores open 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. Our results suggest that the mechanism of action of Arg-9 peptides involves the creation of transient pores in lipid bilayers and cell membranes.
format Articulo
Articulo
author Herce, H. D.
Garcia, A. E.
Litt, J.
Kane, R. S.
Martín, Pedro
Enrique, Nicolás Jorge
Rebolledo, Alejandro
Milesi, Verónica
author_facet Herce, H. D.
Garcia, A. E.
Litt, J.
Kane, R. S.
Martín, Pedro
Enrique, Nicolás Jorge
Rebolledo, Alejandro
Milesi, Verónica
author_sort Herce, H. D.
title Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
title_short Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
title_full Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
title_fullStr Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
title_full_unstemmed Arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
title_sort arginine-rich peptides destabilize the plasma membrane, consistent with a pore formation translocation mechanism of cell-penetrating peptides
publishDate 2009
url http://sedici.unlp.edu.ar/handle/10915/82765
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bdutipo_str Repositorios
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