Charge-dependent translocation of the Trojan peptide penetratin across lipid membranes.
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, X(PG), 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 z(P) approximately 5.1 +/- 0.5. The peptide first binds to the outer surface of the vesicles, the effective binding capacity of which increases with X(PG). At X(PG) approximately 0.5 and a molar ratio of bound peptide-to-lipid of approximately 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
Hans
H
Department of Biophysical Chemistry, Umeå University, SE-90187 Umeå, Sweden. binder@rz.uni-leipzig.de
Lindblom
Göran
G
D002151:Calorimetry / Q000379:methods*; D002352:Carrier Proteins / Q000737:chemistry*; D057846:Cell-Penetrating Peptides; D004735:Energy Transfer; D008051:Lipid Bilayers / Q000737:chemistry*; D008081:Liposomes / Q000737:chemistry*; D008560:Membrane Fluidity; D008567:Membranes, Artificial; D009038:Motion; D010455:Peptides / Q000737:chemistry; D011485:Protein Binding; D055672:Static Electricity
D002352:Carrier Proteins; D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D008081:Liposomes; D008567:Membranes, Artificial; D010455:Peptides; C414409:penetratin