Detecting the insoluble protein aggregates in live cells using an AIE derivative of fluorescent protein chromophore

Many incurable or unmanageable human protein conformational diseases are associated with the misfolding or aggregation of the aberrantly processed or mutant proteins. In this work, we report an aggregation-induced emission (AIE) derivative of fluorescent protein chromophore used to detect the insoluble protein aggregates in live cells. Based on the 4-hydroxybenzylidene-imidazolinone (HBI), we designed and synthesized a series of AIEgens that span a wide range of viscosity coefficients (χ), thus mimicking the viscous microenvironment of a wide variety of amorphous protein aggregates. The mechanism of these AIEgens were systematically investigated using a combination of photophysical studies, computational analyses and structure-function studies. With the aid of the AggTag method, the optimized probe was used to realize the imaging of the aggregated proteome under the control of the proteostasis network. Besides, we also described the formation and decomposition of protein aggregates under the control of small molecule proteostasis regulators. Briefly, we developed a series of AIEgens that explore varying viscosity sensitivities to visualize protein aggregation in live cells as well as study other biological processes that associated with local viscosity changes.