Amyloid-Induced Unzipping of Clustering-Triggered Emission in Water-Soluble Nonconjugated Homopolymer

The design of red-emissive nonconjugated polymers and the interpretation of their photophysical behavior remain a significant challenge in materials chemistry. Clustering-triggered emission (CTE), driven by through-space donor–acceptor (D–A) interactions within polymeric assemblies, is a key principle governing such nonconventional luminescence. Herein, we uncover an unusual red emission from a maleimide-based homopolymer ( PM ) in aqueous media, arising through CTE. Introduction of in vitro synthesized insulin amyloid fibrils (IAFs) directs this emissive polymer into an OFF-pathway, effectively suppressing its ON-state CTE. Fluorescence spectroscopic studies reveal that PM functions as a ratiometric probe for IAFs, where the β-sheet fibril architecture modulates CTE through supramolecular interactions and disrupted clustering. Complementary molecular dynamics (MD) simulations further demonstrate that the emission arises from a delicate balance of intra- and intermolecular interactions within polymer clusters, which become perturbed upon amyloid binding. Together, these findings provide mechanistic insight into CTE in nonconjugated systems and establish a foundation for developing water-soluble luminescent probes for selective amyloid detection and broader biomedical applications.