title: Strain-Promoted Thiol-Mediated Cellular Uptake of Giant Substrates: Liposomes and Polymersomes.
abstract: Simple cyclic disulfides under high tension mediate the uptake of giant substrates, that is, liposomes and polymersomes with diameters of up to 400 nm, into HeLa Kyoto cells. To place them at the surface of the vesicles, the strained disulfides were attached to the head-group of cationic amphiphiles. Bell-shaped dose response curves revealed self-activation of the strained amphiphiles by self-assembly into microdomains at low concentrations and self-inhibition by micelle formation at high concentrations. Poor colocalization of internalized vesicles with endosomes, lysosomes, and mitochondria indicate substantial release into the cytosol. The increasing activity with disulfide ring tension, inhibition with Ellman's reagent, and inactivity of maleimide and guanidinium controls outline a distinct mode of action that deserves further investigation and is promising for practical applications.
authors.affiliation: School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.|National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chuard
authors.affiliation: School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.|Current address: Firmenich SA, Division of Research and Development, Geneva, Switzerland.
authors.forename: Giulio
authors.initials: G
authors.lastname: Gasparini
authors.affiliation: School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Moreau
authors.affiliation: National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.|Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Samuel
authors.initials: S
authors.lastname: Lörcher
authors.affiliation: National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.|Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Palivan
authors.affiliation: National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.|Department of Chemistry, University of Basel, Basel, Switzerland.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meier
authors.affiliation: School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.|National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.
authors.forename: Naomi
authors.initials: N
authors.lastname: Sakai
authors.affiliation: School of Chemistry and Biochemistry, University of Geneva, Geneva, Switzerland.|National Centre of Competence in Research (NCCR) Molecular Systems Engineering, Switzerland.
authors.forename: Stefan
authors.identifier: 0000-0002-8537-8349
authors.initials: S
authors.lastname: Matile
mesh_terms: D006367:HeLa Cells; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D010316:Particle Size; D011108:Polymers / Q000737:chemistry / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism*; D013499:Surface Properties
chemical_list: D008081:Liposomes; D011108:Polymers; D013438:Sulfhydryl Compounds
keywords: cellular uptake; disulfides; liposomes; polymersomes; ring tension