Cholesterol Influence on the Interaction of Cell Penetrating Peptides (CPPs) with Model Membranes

Abstract

A number of high efficiency peptidic transporters are known, which are called CPPs, and which use three mechanisms of cell incorporation. The models proposed to explain the direct translocation of CPPs across biological membranes include the “inverted micelle model”, models involving the formation of membrane pores and the “carpet model”1. Studies have demonstrated that cholesterol prevents interaction of the cell-penetrating peptide transportan with model lipid membranes2. Other studies show that higher cholesterol content and tighter packing of the membrane predominantly reduces accumulation of transportan, TP10 and the model amphipathic peptide (MAP) in vesicles, indicating that the internalization of CPPs takes place preferentially via the more dynamic membrane regions3. Our circular dichroism results show a change in the secondary structure of the peptides upon interaction with model membranes. In addition, fluorescence spectroscopy studies have demonstrated changes in the interaction of peptides with LUV ternary mixtures of DMPC/DMPG/CHO as a function of the cholesterol content.Acknowledgements: We thank Project FONDECYT 1140800 for funding and CONICYT for the PhD scholarship for VSS.1.Trabulo S., Cardoso A.L., Mano M., y Pedroso de Lima M.C., Pharmaceuticals 3, 961-993 (2010).2.Arsov1 Z., Nemec1 M., Schara1 M., Johansson H., Langel U. y Zorko M., Journal of Peptide Science 14(12), 1303-1308 (2008).3.Paea J., Saalikb P., Liivamagia L., Lubenetsa D., Arukuuskc P., Langelc U. y Pooga M. Journal of Controlled Release 192, 103-113 (2014).