Biology – Quantitative Biology – Biomolecules
Scientific paper
2009-10-09
Biophysical Journal, Volume 97, Issue 7, 7 October 2009, Pages 1917-1925
Biology
Quantitative Biology
Biomolecules
This is an extended version of the published manuscript, which had to be shortened before publication to fit within the number
Scientific paper
10.1016/j.bpj.2009.05.066
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.
Enrique N.
Garcia Angel E.
Herce Henry D.
Kane Sharad R.
Litt J.
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