Clustering and binding of oleanolic acid saponins with bacterial membranes.

Abstract

Oleanolic acid saponins are the most common and important triterpenoid saponins in the plant kingdom. They have received extensive attention for their potential medicinal value. Recent studies showed that their biological activities are closely mediated by interaction with lipid bilayers. Previous studies characterized the effect of hydrophilicity on the interactions of saponin with a bacterial membrane model. The amphiphilic nature of these compounds easily drives the formation of large clusters. On the other hand, some saponins contain carboxyl groups, which can be deprotonated at physiological pH. Both aggregation and deprotonation affect saponin-bilayer interactions. To study these interactions, we used molecular dynamics (MD) simulations to probe the effect of chemical structure and concentration on the interaction of four model saponins with a lipid bilayer. Cluster size and hydrophilicity directly impact the degree of binding and insertion of saponin into the bilayer. Large clusters can bind the bilayer and remain intact at the membrane interface in the remaining of the simulation; whereas hydrophobic interactions with the membrane interior play a key role in the insertion and dissociation of small saponin clusters. In addition, we examined the effect of deprotonation of carboxyl groups at different positions in the saponin molecules, which significantly changes their hydrophilicity and interaction mechanism with the lipid bilayer. Taken together, these results increase our understanding of saponin-lipid interactions that are relevant in the study of lipid membrane disruption and rupture as it pertains to antibacterial treatments.