1. J Biol Chem. 2013 May 17;288(20):14000-17. doi: 10.1074/jbc.M112.407635. Epub
2013 Mar 25.

Induction of Highly Curved Structures in Relation to Membrane Permeabilization
and Budding by the Triterpenoid Saponins, α- and δ-Hederin.

Lorent J, Le Duff CS, Quetin-Leclercq J, Mingeot-Leclercq MP.

From Cellular and Molecular Pharmacology and.

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.

PMCID: PMC3656259 [Available on 2014/5/17]
PMID: 23530040  [PubMed - in process]