Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 20, Issue 18, Pages -Publisher
MDPI
DOI: 10.3390/ijms20184441
Keywords
cell-penetrating peptide; peptide-lipid interaction; lipid model systems; molecular dynamics; NMR; membrane biophysics
Funding
- French Ministere de l'Enseignement Superieur et de la Recherche
- La Ligue contre le Cancer
- French National Research Agency (ANR) [ANR-CROSS ANR17-CE11-0050-01]
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Cell-penetrating peptides (CPPs) are short peptides that can translocate and transport cargoes into the intracellular milieu by crossing biological membranes. The mode of interaction and internalization of cell-penetrating peptides has long been controversial. While their interaction with anionic membranes is quite well understood, the insertion and behavior of CPPs in zwitterionic membranes, a major lipid component of eukaryotic cell membranes, is poorly studied. Herein, we investigated the membrane insertion of RW16 into zwitterionic membranes, a versatile CPP that also presents antibacterial and antitumor activities. Using complementary approaches, including NMR spectroscopy, fluorescence spectroscopy, circular dichroism, and molecular dynamic simulations, we determined the high-resolution structure of RW16 and measured its membrane insertion and orientation properties into zwitterionic membranes. Altogether, these results contribute to explaining the versatile properties of this peptide toward zwitterionic lipids.
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