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

Author(s)

Weinberger, Andreas ; Walter, Vivien ; MacEwan, Sarah R. ; Schmatko, Tatiana ; Muller, Pierre ; Schroder, Andre P. ; Chilkoti, Ashutosh ; Marques, Carlos M.

• Document type: Journal article
• Source: SCIENTIFIC REPORTS; v. 7, MAR 6 2017.
• Web of Science Citations: 5

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. (AU)

• FAPESP's process: 15/07508-5 - The influence of photo-induced oxidation on peptide-membrane interactions
• Grantee: Mauricio da Silva Baptista
• Support Opportunities: Research Grants - Visiting Researcher Grant - International