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Significance There is growing evidence suggesting that intracellular phase transitions play roles in biological functions. However, little is known about phase transitions of lipid droplets that are organelles involved in energy homeostasis. Here, we demonstrate a universal intracellular phase diagram of lipid droplets, consistent with the in vitro phase diagram, and reveal that cholesterol esters cause the liquid–liquid crystal phase transition under near-physiological conditions. We moreover combine in vivo and in vitro studies, together with the theory of confined liquid crystals, to suggest that the radial molecular alignments in the liquid crystallized lipid droplets are caused by an anchoring force at the droplet surface. These findings pave the way for a better understanding of their biological functions and diseases.

Universal phase behaviors of intracellular lipid droplets