Translocation of the Cell Penetrating Peptide Penetratin through Asymmetric Model Membranes Formed by a Microfluidic Device: Role of the Lipids and Transmembrane Potential

Self-assembly and intracellular delivery of DNA by a truncated fragment derived from theTrojanpeptidePenetratin

“…In addition, KIW7 conserves main features of Penetratin secondary structure, including random-to- transitions upon interaction with anionic surfactant interfaces, thus suggesting that structuration of Penetratin in the presence of biomembranes (a key feature for translocation capacity) is closely correlated to the uncharged residues preserved in the truncated peptide. Although the role of non-polar amino acids for bioactivity of Trojan peptides, specially tryptophan residues, has received increasingly attention in recent years, 20,35,69 the importance of cationic residues has been the main focus. In this context, the findings presented here undoubtably demonstrate that non-cationic amino acids are directly implicated in cell uptake and, even in the absence of strong cationicity, they make intracell delivery of DNA fragments feasible.…”

“…In contrast, it also displays a few hydrophobic amino acids that lead to a "dual mode" of interaction with lipid membranes. 19,20 The ability of Penetratin to form ordered aggregates in the presence of anionic surfactants has motivated the study of the synergism between this peptide and lipids. 19,21,22 Although understanding on the exact mechanisms by which Penetratin translocates cell membranes is a still evolving process, it has been shown that interaction with negatively-charged phospholipids is mainly driven by electrostatic attraction, followed by limited insertion of peptide into bilayers.…”