(608f) Interaction of Amphiphilic Molecules with Lipid Membrane Models

Lipids are amphiphilic molecules that self-assemble into a bilayer with a hydrophilic surface and hydrophobic core. The lipid bilayer is an important semi-permeable structure present in all cells of living organisms. Previous studies show lipids are critical to the function and structure of membrane proteins and directly control the translocation of small molecules through the membrane. Interestingly, natural molecules, such as saponins, can kill bacteria by disrupting their membrane structures. Saponins are amphiphilic molecules similar to lipids have attracted widespread attention for their potential medicinal value, they are made by sugar groups attached to a hydrophobic aglycone. Characterizing the interaction mechanisms between saponins and membrane lipids will provide insights into the behavior of amphiphilic molecules at the membrane interface. We used molecular dynamics simulations to probe the interaction of four model saponins with a generic bacterial membrane model at the atomistic level. The selected saponins share an aglycone structure but differ in their sugar chains, which alters their hydrophobicity. Our results show the more hydrophobic saponins interact more strongly with lipid bilayers, inserting deeply into the membrane hydrophobic core. On the other hand, hydrophilic saponins locate horizontally at the lipid/water interface and do not penetrate the bilayer. We also examined the effect of deprotonation of carboxyl groups at different positions in the saponin molecules. Results show that deprotonation site affects interactions with the bilayer by modulating hydrophilicity of the molecules. Finally, these simulations characterized the impact of saponin-lipid interactions on bilayer structure and properties, including order parameters, tilt angle of lipid tails, lateral pressure profiles, surface defects, and line tension. Taken together, our simulations increase our understanding of the interaction of small molecules with membranes at the molecular-level.