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Interaction of S4 13 ‐PV cell penetrating peptide with model membranes: relevance to peptide translocation across biological membranes
Author(s) -
Mano Miguel,
Henriques Ana,
Paiva Artur,
Prieto Manuel,
Gavilanes Francisco,
Simões Sérgio,
De Lima Maria C. Pedroso
Publication year - 2007
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.842
Subject(s) - membrane , peptide , chemistry , cell penetrating peptide , biological membrane , chromosomal translocation , cell , biophysics , cell membrane , microbiology and biotechnology , biochemistry , biology , gene
Cell penetrating peptides (CPPs) have been successfully used to mediate the intracellular delivery of a wide variety of molecules of pharmacological interest both in vitro and in vivo , although the mechanisms by which the cellular uptake occurs remain unclear and controversial. Following our previous work demonstrating that the cellular uptake of the S4 13 ‐PV CPP occurs mainly through an endocytosis‐independent mechanism, we performed a detailed biophysical characterization of the interaction of this peptide with model membranes. We demonstrate that the interactions of the S4 13 ‐PV peptide with membranes are essentially of electrostatic nature. As a consequence of its interaction with negatively charged model membranes, the S4 13 ‐PV peptide becomes buried into the lipid bilayer, which occurs concomitantly with significant peptide conformational changes that are consistent with the formation of a helical structure. Comparative studies using two related peptides demonstrate that the conformational changes and the extent of cell penetration are dependent on the peptide sequence, indicating that the helical structure acquired by the S4 13 ‐PV peptide is relevant for its nonendocytic uptake. Overall, our data suggest that the cellular uptake of the S4 13 ‐PV CPP is a consequence of its direct translocation through cell membranes, following conformational changes induced by peptide‐membrane interactions. Copyright © 2007 European Peptide Society and John Wiley & Sons, Ltd.