The role of Cell Penetrating Peptides (CPPs) in membrane lipid phase behavior: a novel aspect elucidating peptide-mediated delivery
Cell Penetrating Peptides (CPPs) constitute a class of short cationic peptides, which share the ability to deliver therapeutic agents (proteins, oligonucleotides) into target cells. The mechanisms proposed for the CPPs cellular uptake (endocytic, endosomal escape, etc.) are still controversial.
In the hypothesis that membrane lateral heterogeneity generated by multi lipid and protein components in cell membrane could play an important role in CPPs translocation process, we conducted studies on two popular CPPs, penetratin (RQIKIWFQNRRMKWKK)  and pep-1 (KETWWETWWTEWSQPKKKRKV) , in the presence of giant unilamellar vesicles (GUVs). In particular, we used GUVs containing different quaternary mixtures of 1,2-Dioleoyl-sn-Glycero-3-Phosphocholine (DOPC), 1,2-Dipalmitoyl-sn-Glycero-3-Phosphocholine (DPPC), Cholesterol (Chol), 1,2-Dipalmitoyl-sn-Glycero-3-[Phospho-rac-(1-glycerol)] (Sodium Salt) (DPPG) and showing liquid-liquid fluid phase coexistence, which provides an...
KeywordsLipid Raft Phase Coexistence Endosomal Escape Translocation Process Giant Unilamellar Vesicle