title: Induction of highly curved structures in relation to membrane permeabilization and budding by the triterpenoid saponins, α- and δ-Hederin.
abstract: The interactions of triterpenoid monodesmosidic saponins, α-hederin and δ-hederin, with lipid membranes are involved in their permeabilizing effect. Unfortunately, the interactions of these saponins with lipid membranes are largely unknown, as are the roles of cholesterol or the branched sugar moieties (two for α-hederin and one for δ-hederin) on the aglycone backbone, hederagenin. The differences in sugar moieties are responsible for differences in the molecular shape of the saponins and the effects on membrane curvature that should be the most positive for α-hederin in a transbilayer direction. In large unilamellar vesicles and monocyte cells, we showed that membrane permeabilization was dependent on the presence of membrane cholesterol and saponin sugar chains, being largest for α-hederin and smallest for hederagenin. In the presence of cholesterol, α-hederin induced the formation of nonbilayer phases with a higher rate of Brownian tumbling or lateral diffusion. A reduction of Laurdan's generalized polarization in relation to change in order of the polar heads of phospholipids was observed. Using giant unilamellar vesicles, we visualized the formation of wrinkled borders, the decrease in liposome size, budding, and the formation of macroscopic pores. All these processes are highly dependent on the sugars linked to the aglycone, with α-hederin showing a greater ability to induce pore formation and δ-hederin being more efficient in inducing budding. Hederagenin induced intravesicular budding but no pore formation. Based on these results, a curvature-driven permeabilization mechanism dependent on the interaction between saponin and sterols and on the molecular shape of the saponin and its ability to induce local spontaneous curvature is proposed.
authors.affiliation: Cellular and Molecular Pharmacology, Université Catholique de Louvain, B-1200 Bruxelles; Pharmacognosy, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Bruxelles.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lorent
authors.affiliation: Molecules, Solids and Reactivity, Institute of Condensed Matter and Nanosciences, Université Catholique de Louvain, B-1348 Louvain-la-Neuve, Belgium.
authors.forename: Cécile S
authors.initials: CS
authors.lastname: Le Duff
authors.affiliation: Pharmacognosy, Louvain Drug Research Institute, Université Catholique de Louvain, B-1200 Bruxelles.
authors.forename: Joelle
authors.initials: J
authors.lastname: Quetin-Leclercq
authors.affiliation: Cellular and Molecular Pharmacology, Université Catholique de Louvain, B-1200 Bruxelles. Electronic address: marie-paule.mingeot@uclouvain.be.
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Mingeot-Leclercq
mesh_terms: D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000737:chemistry*; D002463:Cell Membrane Permeability; D002784:Cholesterol / Q000737:chemistry; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008564:Membrane Potentials; D008856:Microscopy, Fluorescence; D008956:Models, Chemical; D009000:Monocytes / Q000166:cytology; D009828:Oleanolic Acid / Q000031:analogs & derivatives* / Q000737:chemistry; D012503:Saponins / Q000737:chemistry*; D013261:Sterols / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D008051:Lipid Bilayers; D012503:Saponins; D013261:Sterols; C010177:beta-hederin; D009828:Oleanolic Acid; D002784:Cholesterol; C025763:hederagenin
keywords: Curvature; Lipid Phase; Liposomes; Membrane Bilayer; Membrane Biophysics; Membrane Lipids; Permeabilization; Saponin; Sterol; α-Hederin