Water-Soluble Conjugated Polymers for the Detection and Inhibition of Protein Aggregation

Protein aggregation is etiologically associated with a wide range of devastating neurodegenerative diseases such as Alzheimer's and prion diseases, and therefore the new strategies for the detection and inhibition of protein aggregation are urgently desired. Herein, the capability of a cationic water-soluble poly(phenylene vinylene) derivative (PPV-NMe3+) to detect and inhibit the protein aggregation has been explored, using the hen egg white lysozyme (HEWL) as a model system whose aggregation is triggered by UV illumination. The PPV-NMe3+ binds efficiently to the surface of the HEWL aggregates driven by the hydrophobic interactions, leading to the reduction of interchain contacts and therefore the enhancement of fluorescence intensity of the conjugated polymer. Importantly, the hydrophobic interactions between HEWL and PPV-NMe3+ compete with the interaction that dominates the formation of the HEWL self-assembly, and the electrostatic repulsion between the neighboring PPV-NMe3+-coated aggregates reduces and inhibits the further aggregation of HEWL. In this way, the water-soluble conjugated polymer PPV-NMe3+ serves as both the detector and inhibitor for the protein aggregation triggered by UV illumination, which promises advanced potential applications in the diagnose and prevention of diseases caused by protein aggregation.