Kinetically Controlled Self-Assembly of a Lipophilic Fluorophore with Phenylalanine-based Diamides in Artificial Lipid Droplets

Lipid droplets (LDs) are vital organelles that govern energy storage and lipid metabolism in cells. The ability to direct the self-assembly of small molecules into defined nanostructures within LDs would provide opportunities to modulate their functions. Although supramolecular polymerization has been extensively investigated in low-polarity media, achieving controlled molecular assembly in neutral lipid droplets remains a formidable challenge. Here, we report the design of a lipophilic donor–acceptor-type fluorophore bearing phenylalanine-derived diamide units, which undergoes controlled supramolecular polymerization in the neutral lipid triolein. In triolein, the molecule assembles into fibrous aggregates that display intense fluorescence and a pronounced Cotton effect in circular dichroism spectrum. Spectroscopic and microscopic analyses reveal that a seeding strategy accelerates the conversion from a kinetically trapped monomeric state to fibrous assemblies. Furthermore, fluorescence imaging in artificial LDs demonstrates that aggregate size can be tuned through the seeding process.