Phenylalanine-Based Hydrophobic Carbon Dots for Lipid-Phase-Dependent Emission and Detection of Biomolecular Self-Assembled Structures

Abstract

The cellular membrane, composed of lipids, plays a critical role in preserving cellular integrity and facilitating numerous essential cellular processes. To shed light on lipid membrane dynamics, including lipid bilayer fluidity, lipid phase behavior, lipid movement, and biomolecular diffusion, several fluorescent-dye-based bioanalytical approaches have been adopted over time. However, conventional fluorescent dyes have several limitations, such as inefficient insertion into lipid bilayers, low fluorescence intensity, and rapid photobleaching, among others. In this aspect, carbon dots can be promising candidates and a possible replacement for conventional dyes. But the literature lacks reports on biomolecule-derived carbon dots that can distinguish between lipid phase behaviors. In this present work, we focus on an innovative and unique application of a phenylalanine-based hydrophobic carbon dot (FHCD). It showcases quite a remarkable and distinct emission when embedded in both ordered and disordered lipid membranes, which could be utilized to probe the lipid phase behavior. Additionally, FHCD can also successfully capture biomolecular self-assembly as well as detect metastable intermediates and membraneless biomolecular condensates. This work can further pave the way in designing other synthetic probes to monitor the lipid membrane dynamics as well as the biomolecular self-assembly. © 2025 American Chemical Society