The Action of Alpha Hederin, a Triperpenoid Saponin, on Membranes

Abstract

α-hederin is a triterpenoid saponin which has shown hemolytic and apoptotic properties. (Chwalek et al. 2006, Gauthier et al. 2009). Many saponins are known to interact with biological membranes on a cholesterol dependent or independent manner (Francis et al. 2002) but the underlying mechanisms need to be further explored. We have studied the effects of α-hederin on size, membrane permeability and fluidity in a LUV model composed of DMPC including 25% (mol/mol) of cholesterol or not. Size was determined by quasi-elastic light scattering spectroscopy. Permeability was evaluated by the release of calcein, entrapped at self-quenching concentrations in liposomes. Membrane dynamics at the hydrophobic core was evaluated by fluorescence anisotropy of diphenylhexatriene, upon increasing temperatures.α-hederin increased the size of cholesterol-rich liposomes and induced release of calcein entrapped within liposomes, on a time- and concentration-dependent manner. It was without effect when cholesterol was absent. α-hederin reduced the transition temperature on a concentration-dependent manner only in liposomes containing cholesterol but increased anisotropy beyond the transition temperature in both types of liposomes.Our data suggest that cholesterol is required for α-hederin's effects on liposome's size, permeability and transition temperature but probably not for the effect on membrane fluidity, when lipids are in fluid phase. The role of these effects for apoptosis induced by α-hederin is under investigation.