1. Langmuir. 2014 Apr 29;30(16):4556-69. doi: 10.1021/la4049902. Epub 2014 Apr 14.

Domain Formation and Permeabilization Induced by the Saponin α-Hederin and Its
Aglycone Hederagenin in a Cholesterol-Containing Bilayer.

Lorent J(1), Lins L, Domenech O, Quetin-Leclercq J, Brasseur R, Mingeot-Leclercq 

Author information: 
(1)Université Catholique de Louvain , Louvain Drug Research Institute, Cellular and 
Molecular Pharmacology, B1.73.05, Avenue E. Mounier 73, B-1200 Brussels, Belgium.

Saponins and triterpenic acids have been shown to be able to interact with lipid 
membranes and domains enriched with cholesterol (rafts). How saponins are able to
modulate lipid phase separation in membranes and the role of the sugar chains for
this activity is unknown. We demonstrate in a binary membrane model composed of
DMPC/Chol (3:1 mol/mol) that the saponin α-hederin and its aglycone presenting no
sugar chain, the triterpenic acid hederagenin, are able to induce the formation
of lipid domains. We show on multilamellar vesicles (MLV), giant unilamellar
vesicles (GUV), and supported planar bilayers (SPB) that the presence of sugar
units on the sapogenin accelerates domain formation and increases the proportion 
of sterols within these domains. The domain shape is also influenced by the
presence of sugars because α-hederin and hederagenin induce the formation of
tubular and spherical domains, respectively. These highly curved structures
should result from the induction of membrane curvature by both compounds. In
addition to the formation of domains, α-hederin and hederagenin permeabilize GUV.
The formation of membrane holes by α-hederin comes along with the accumulation of
lipids into nonbilayer structures in SPB. This process might be responsible for
the permeabilizing activity of both compounds. In LUV, permeabilization by
α-hederin was sterol-dependent. The biological implications of our results and
the mechanisms involved are discussed in relation to the activity of saponins and
triterpenic acids on membrane rafts, cancer cells, and hemolysis.

PMID: 24690040  [PubMed - in process]