S4(13)-PV cell-penetrating peptide induces physical and morphological changes in membrane-mimetic lipid systems and cell membranes: Implications for cell internalization

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Ana M S Cardoso (Author) Other; Sara Trabulo (Author) Other; Ana L Cardoso (Author) Other; Annely Lorents (Author) Other; Catarina M Morais (Author) Other; Paula Gomes (Author) FCUP; Claudia Nunes (Author) Other; Marlene Lucio (Author) FFUP; Salette Reis (Author) FFUP; Kaert Padari (Author) Other; Margus Pooga (Author) Other; Maria C P Pedroso de Lima (Author) Other; Amalia S Jurado (Author) Other

Journal

Title: Biochimica et Biophysica Acta: Biomembranes

Vol. 1818

Pages: 877-888

ISSN: 0005-2736

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 37 Citations

Scopus - 37 Citations

Scientific classification

FOS: Natural sciences > Biological sciences

Other information

Authenticus ID: P-002-CM7

DOI: 10.1016/j.bbamem.2011.12.022

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific