A Solvatochromic Fluorescent Probe Reveals Polarity Heterogeneity upon Protein Aggregation in Cells
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- Wang Wan
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Lianggang Zeng
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Wenhan Jin
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Xinxin Chen
- National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences 15 Datun Road, Chaoyang District Beijing 100101 China
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- Di Shen
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Yanan Huang
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Mengdie Wang
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Yulong Bai
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Haochen Lyu
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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- Xuepeng Dong
- The Second Hospital of Dalian Medical University 467 Zhongshan Road 116023 China Dalian
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- Zhenming Gao
- The Second Hospital of Dalian Medical University 467 Zhongshan Road 116023 China Dalian
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- Lei Wang
- National Laboratory of Biomacromolecules CAS Center for Excellence in Biomacromolecules Institute of Biophysics Chinese Academy of Sciences 15 Datun Road, Chaoyang District Beijing 100101 China
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- Xiaojing Liu
- Institute of Molecular Sciences and Engineering Shan Dong University 72 Binhai Road Qingdao 266237 China
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- Yu Liu
- CAS Key Laboratory of Separation Science for Analytical Chemistry Dalian Institute of Chemical Physics Chinese Academy of Sciences 457 Zhongshan Road Dalian 116023 China
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<jats:title>Abstract</jats:title><jats:p>We report a crystallization‐induced emission fluorophore to quantitatively interrogate the polarity of aggregated proteins. This solvatochromic probe, namely “AggRetina” probe, inherently binds to aggregated proteins and exhibits both a polarity‐dependent fluorescence emission wavelength shift and a viscosity‐dependent fluorescence intensity increase. Regulation of its polarity sensitivity was achieved by extending the conjugation length. Different proteins bear diverse polarity upon aggregation, leading to different resistance to proteolysis. Polarity primarily decreases during protein misfolding but viscosity mainly increases upon the formation of insoluble aggregates. We quantified the polarity of aggregated protein‐of‐interest in live cells via HaloTag bioorthogonal labeling, revealing polarity heterogeneity within cellular aggregates. The enriched micro‐environment details inside misfolded and aggregated proteins may correlate to their bio‐chemical properties and pathogenicity.</jats:p>
収録刊行物
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- Angewandte Chemie International Edition
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Angewandte Chemie International Edition 60 (49), 25865-25871, 2021-11-02
Wiley
