Liquid-crystalline phase transitions in lipid droplets are related to cellular states and specific organelle association

Significance Lipids have essential roles in cellular energy homeostasis and are key structural components of membranes and thereby provide the basis of cellular compartmentalization. The maintenance of lipid homeostasis is of fundamental importance to cellular physiology. Lipid droplets (LDs) are central organelles orchestrating lipid fluxes inside cells. By examining pristinely preserved frozen-hydrated HeLa cells with cryoelectron microscopy, we show that LDs exhibit different internal organizations, as well as organelle associations, depending on cellular states. We demonstrate the presence of a liquid-crystalline phase under certain conditions, which are likely to impact the physiological functions of LDs. Furthermore, crystalline droplets are a major component of atherosclerotic lesions in human arteries. Crystalline LDs secreted by cells may therefore have a direct link to pathologies.