Fluorogenic sensing of amorphous aggregates, amyloid fibers, and chaperone activity via a near‐infrared aggregation‐induced emission‐active probe
Wei He,
Yuanyuan Yang,
Yuhui Qian,
Zhuoyi Chen,
Yongxin Zheng,
Wenping Zhao,
Chenxu Yan,
Zhiqian Guo,
Shu Quan
Affiliations
Wei He
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Yuanyuan Yang
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Yuhui Qian
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Zhuoyi Chen
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Yongxin Zheng
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Wenping Zhao
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Chenxu Yan
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Frontiers Science Center for Materiobiology and Dynamic Chemistry Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China
Zhiqian Guo
Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Shanghai Key Laboratory of Functional Materials Chemistry Frontiers Science Center for Materiobiology and Dynamic Chemistry Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology Shanghai China
Shu Quan
State Key Laboratory of Bioreactor Engineering Shanghai Collaborative Innovation Center for Biomanufacturing (SCICB) East China University of Science and Technology Shanghai China
Abstract The presence of protein aggregates in numerous human diseases underscores the significance of detecting these aggregates to comprehend disease mechanisms and develop novel therapeutic approaches for combating these disorders. Despite the development of various biosensors and fluorescent probes that selectively target amyloid fibers or amorphous aggregates, there is still a lack of tools capable of simultaneously detecting both types of aggregates. Herein, we demonstrate the quantitative discernment of amorphous aggregates by QM‐FN‐SO3, an aggregation‐induced emission (AIE) probe initially designed for detecting amyloid fibers. This probe easily penetrates the membranes of the widely‐used prokaryotic model organism Escherichia coli, enabling the visualization of both amorphous aggregates and amyloid fibers through near‐infrared fluorescence. Notably, the probe exhibits sensitivity in distinguishing the varying aggregation propensities of proteins, regardless of whether they form amorphous aggregates or amyloid fibers in vivo. These properties contribute to the successful application of the QM‐FN‐SO3 probe in the subsequent investigation of the antiaggregation activities of two outer membrane protein (OMP) chaperones, both in vitro and in their physiological environment. Overall, our work introduces a near‐infrared fluorescent chemical probe that can quantitatively detect amyloid fibers and amorphous aggregates with high sensitivity in vitro and in vivo. Furthermore, it demonstrates the applicability of the probe in chaperone biology and its potential as a high‐throughput screening tool for protein aggregation inhibitors and folding factors.
