Induction of highly curved structures in relation to membrane permeabilization and budding by the triterpenoid saponins, α- and δ-Hederin.
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.
['Lorent|Joseph|J|', 'Le Duff|Cécile S|CS|', 'Quetin-Leclercq|Joelle|J|', 'Mingeot-Leclercq|Marie-Paule|MP|']
D045744:Cell Line, Tumor D002462:Cell Membrane D002463:Cell Membrane Permeability D002784:Cholesterol D006801:Humans D008051:Lipid Bilayers D009682:Magnetic Resonance Spectroscopy D008564:Membrane Potentials D008856:Microscopy, Fluorescence D008956:Models, Chemical D009000:Monocytes D009828:Oleanolic Acid D012503:Saponins D013261:Sterols D013696:Temperature D013997:Time Factors
Permeabilization Saponin α-Hederin Curvature Liposomes Sterol Lipid Phase Membrane Bilayer Membrane Biophysics Membrane Lipids