Abstract
Mechanical cues from both the extracellular environment and intracellular structures play a crucial role in liver cancer. In conditions like fibrosis and hepatocellular carcinoma (HCC), increased tissue stiffness affects cellular processes such as migration, proliferation, and chemoresistance. Lipid droplets (LDs), key modulators of cellular stress, contribute to nuclear deformation, cytoskeletal reorganization, and metabolic disruption, though the mechanisms remain unclear. This project investigates the impact of extracellular (substrate stiffness) and intracellular (LD-induced stress) forces on liver cancer cell function at the single-cell and sub-cellular levels. We hypothesize that mechanical disruption of organelles, particularly via LDs, alters cellular fate by affecting gene expression, organelle positioning, and biophysical processes. Using advanced 2D and 3D cell cultures, we aim to uncover how LD-driven mechanical stress modulates liver cancer cell functions and reveal potential therapeutic targets for HCC progression.