# Kinetically Controlled Self‐Assembly of a Lipophilic Fluorophore with Phenylalanine‐Based Diamides in Artificial Lipid Droplets

## TL;DR

Researchers designed a fluorophore that self-assembles into fibrous structures in artificial lipid droplets, enabling control over aggregate size through a seeding strategy.

## Contribution

A lipophilic fluorophore with phenylalanine-based diamides enables controlled supramolecular polymerization in artificial lipid droplets.

## Key findings

- The fluorophore forms fibrous aggregates in triolein with intense fluorescence and a Cotton effect.
- A seeding strategy accelerates the transition from a monomeric state to fibrous assemblies.
- Aggregate size in artificial lipid droplets can be tuned using the seeding process.

## Abstract

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.

Fibrous aggregates in triolein are constructed from a lipophilic donor–acceptor fluorophore bearing two phenylalanine‐based diamide units. Spectroscopic analyses and fluorescence imaging revealed a kinetically trapped state persisting for hours, enabling seeded modulation of aggregate size in artificial lipid droplets encapsulating triolein within a surfactant shell.