Cholesteryl Esters Modulate Lipid Droplet Rigidity and Monolayer Organization during Liver Cancer Progression

In mammalian cells, lipid monolayers support the integrity of lipid droplets (LDs), organelles that function as storage sites for neutral lipids. Liver-targeting illnesses such as liver cancer interrupt normal LD metabolism and prompt changes in the chemical content of these organelles, which can have effects on the structural and organizational behavior of the lipids. In LDs, liver cancer induces concentric crystalline phases of cholesteryl esters (CEs) and triglycerides near the neutral lipid-monolayer interface, which become more pronounced as the CE concentration increases. Yet, there is little known about how this phenomenon may link to the persistence of undigested LDs in liver cancer patients. To shed light on this, all-atom molecular dynamics simulations were used to model LD micropipette aspiration experiments and gain insights into the effect of CE concentration on partitioning, structural, and mechanical properties of LDs. We successfully modeled micropipette aspiration by applying constant surface tension laterally, which stretched lipid bilayers and monolayers as the magnitude increased. The results show increased phospholipid packing due to the insertion of CE fatty tails into the monolayer. Increasing CE concentration induces a nonlinear change in surface packing defects on the LDs, notable rigidification, and stiffness. Taken together, these insights improve our understanding of the effect of CE abundance on the physical properties at the LD monolayer-core interface.