A Biocompatible Fluorescent Probe for the Selective Detection of Amyloid Fibrils

The misfolding and aggregation of proteins leading to amyloid formation has been linked to numerous diseases, necessitating the development of tools to monitor the fibrillation process. Here we report an intramolecular charge transfer (ICT) dye, DMNDC, as an alternative to Thioflavin-T (ThT), most commonly used for monitoring amyloid fibrils. Using insulin as a model protein, we show that DMNDC efficiently detects all stages of fibril formation, namely, nucleation, elongation, and saturation. An approximately 70 nm hypsochromic shift along with a large increase in emission intensity was observed upon binding of DMNDC to protein fibrils. The aggregation kinetics of insulin remained unaffected at excess DMNDC concentration, suggesting that DMNDC does not inhibit insulin aggregation. Additionally, the efficient cellular internalization and low toxicity of DMNDC make it highly suited for sensing and imaging of amyloid fibrils in the complex biological milieu.