Please use this identifier to cite or link to this item: https://hdl.handle.net/10216/82115
Author(s): Ana M S Cardoso
Sara Trabulo
Ana L Cardoso
Annely Lorents
Catarina M Morais
Paula Gomes
Claudia Nunes
Marlene Lucio
Salette Reis
Kaert Padari
Margus Pooga
Maria C P Pedroso de Lima
Amalia S Jurado
Title: S4(13)-PV cell-penetrating peptide induces physical and morphological changes in membrane-mimetic lipid systems and cell membranes: Implications for cell internalization
Issue Date: 2012
Abstract: The present work aims to gain insights into the role of peptide-lipid interactions in the mechanisms of cellular internalization and endosomal escape of the S4(13)-PV cell-penetrating peptide, which has been successfully used in our laboratory as a nucleic acid delivery system. A S4(13)-PV analogue, S4(13)-PVscr, displaying a scrambled amino acid sequence, deficient cell internalization and drug delivery inability, was used in this study for comparative purposes. Differential scanning calorimetry, fluorescence polarization and X-ray diffraction at small and wide angles techniques showed that both peptides interacted with anionic membranes composed of phosphatidylglycerol or a mixture of this lipid with phosphatidylethanolamine, increasing the lipid order, shifting the phase transition to higher temperatures and raising the correlation length between the bilayers. However, S4(13)-PVscr, in contrast to the wild-type peptide, did not promote lipid domain segregation and induced the formation of an inverted hexagonal lipid phase instead of a cubic phase in the lipid systems assayed. Electron microscopy showed that, as opposed to S4(13)-PVscr, the wild-type peptide induced the formation of a non-lamellar organization in membranes of HeLa cells. We concluded that lateral phase separation and destabilization of membrane lamellar structure without compromising membrane integrity are on the basis of the lipid-driven and receptor-independent mechanism of cell entry of S4(13)-PV peptide. Overall, our results can contribute to a better understanding of the role of peptide-lipid interactions in the mechanisms of cell-penetrating peptide membrane translocation, helping in the future design of more efficient cell-penetrating peptide-based drug delivery systems.
Subject: Ciências biológicas
Biological sciences
Scientific areas: Ciências exactas e naturais::Ciências biológicas
Natural sciences::Biological sciences
URI: https://repositorio-aberto.up.pt/handle/10216/82115
Document Type: Artigo em Revista Científica Internacional
Rights: openAccess
License: https://creativecommons.org/licenses/by-nc/4.0/
Appears in Collections:FCUP - Artigo em Revista Científica Internacional
FFUP - Artigo em Revista Científica Internacional

Files in This Item:
File Description SizeFormat 
89160.pdf1.88 MBAdobe PDFThumbnail
View/Open


This item is licensed under a Creative Commons License Creative Commons