(169w) Modeling the Effect of Surface Tension and Neutral Lipid Mixtures on the Structure of Lipid Monolayer Interfaces

In mammalian cells, lipid monolayers support the integrity of lipid droplets (LDs), organelles that function as storage for neutral lipids. Liver-targeting illnesses such as hepatitis C, non-alcoholic fatty liver disease and liver cancer interrupt normal lipid droplet metabolism and prompt changes in their chemical, structural and mechanical properties. In recent studies, the structure of LDs has been refined to include concentric crystalline phases of cholesteryl esters (CEs) and triglycerides near the interface where the neutral lipid core meets the lipid monolayer. This packing becomes more pronounced as CE concentration increases, showing a dependence of these structures on neutral lipid mixture. However, there is still need for molecular-level understanding of how lipid content and dynamics facilitate the presence of these structures within LDs. In this work, we use molecular dynamics simulations to model LD systems containing lipid mixtures of increasing CE mass% and evaluate changes in lateral organization and biophysical properties of the neutral core and phospholipid monolayer. To probe mechanical properties of the modelled LDs, we also observe changes under increasing surface tension. The results suggest a competition between (i) decreased ordered packing of the monolayer due to lateral stretching, and (ii) increased lipid packing due to insertion of fatty tails of CE into the monolayer. Stretching prompts vertical compression of the neutral LD core and increased repulsion between molecules at the monolayer-core interface. In addition, the tail end of the CE molecules prefers to localize in the monolayer as CE interdigitation equilibrates. To build on this work, the biophysical and mechanical effects of other key lipid species of LDs will be examined. Taken together with results from our collaborators, our insights improve understanding of the effects of liver diseases on the molecular arrangement and stability of LD monolayer-core interfaces.