title: 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.
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: Andreas
authors.initials: A
authors.lastname: Weinberger
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: Vivien
authors.initials: V
authors.lastname: Walter
authors.affiliation: Duke University, Department of Biomedical Engineering, Durham, North Carolina, USA.
authors.forename: Sarah R
authors.initials: SR
authors.lastname: MacEwan
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Schmatko
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Muller
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: André P
authors.initials: AP
authors.lastname: Schroder
authors.affiliation: Duke University, Department of Biomedical Engineering, Durham, North Carolina, USA.
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Chilkoti
authors.affiliation: Université de Strasbourg, CNRS, ICS UPR 22, F-67000 Strasbourg, France.
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Marques
mesh_terms: D057846:Cell-Penetrating Peptides / Q000378:metabolism*; D008051:Lipid Bilayers / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism*; D018613:Microscopy, Confocal; D011485:Protein Binding
chemical_list: D057846:Cell-Penetrating Peptides; D008051:Lipid Bilayers; D008563:Membrane Lipids