We studied the interaction of the cell-penetrating peptide penetratin with mixed dioleoylphosphatidylcholine/dioleoylphoshatidylglycerol (DOPC/DOPG) unilamellar vesicles as a function of the molar fraction of anionic lipid, XPG, by means of isothermal titration calorimetry. The work was aimed at getting a better understanding of factors that affect the peptide binding to lipid membranes and its permeation through the bilayer. The binding was well described by a surface partitioning equilibrium using an effective charge of the peptide of zp ≈ 5.1 ± 0.5. The peptide first binds to the outer surface of the vesicles, the effective binding capacity of which increases with XPG. At XPG ≈ 0.5 and a molar ratio of bound peptide-to-lipid of ∼1/20 the membranes become permeable and penetratin binds also to the inner monolayer after internalization. The results were rationalized in terms of an "electroporation-like" mechanism, according to which the asymmetrical distribution of the peptide between the outer and inner surfaces of the charged bilayer causes a transmembrane electrical field, which alters the lateral and the curvature stress acting within the membrane. At a threshold value these effects induce internalization of penetratin presumably via inversely curved transient structures.
Binder, H., & Lindblom, G. (2003). Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes. Biophysical Journal, 85(2), 982–995. https://doi.org/10.1016/S0006-3495(03)74537-8