Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes

Abstract

Although cationic cell-penetrating peptides (CPPs) are able to bind to cell membranes, thus promoting cell internalization by active pathways, attachment of cargo molecules to CPPs invariably reduces their cellular uptake. We show here that CPP binding to lipid bilayers, a simple model of the cell membrane, can be recovered by designing cargo molecules that self-assemble into spherical micelles and increase the local interfacial density of CPP on the surface of the cargo. Experiments performed on model giant unilamellar vesicles under a confocal laser scanning microscope show that a family of thermally responsive elastin-like polypeptides that exhibit temperature-triggered micellization can promote temperature triggered attachment of the micelles to membranes, thus rescuing by self-assembly the cargo-induced loss of the CPP affinity to bio-membranes.

Adsorption of cell-penetrating peptides on a vesicle, triggered by temperature (Bottom) as compared to a vesicle without adsorption (Top).

Author(s) & Affilation(s)

Andreas Weinberger¹, Vivien Walter¹, Sarah R. MacEwan², Tatiana Schmatko¹, Pierre Muller¹, André P. Schroder¹, Ashutosh Chilkoti² & Carlos M. Marques¹

1. Université de Strasbourg, CNRS, ICS UPR 22, Strasbourg, F-67000, France
2. Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA

Cite this publication

Weinberger et al., Cargo self-assembly rescues affinity of cell-penetrating peptides to lipid membranes, Sci Rep 2017, 7, 43963

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