中科院大连化学物理研究所刘宇团队在研究中取得进展。他们开发出溶剂变色荧光探针揭示细胞中蛋白质聚集的极性不均一性。2021年9月25日，国际知名学术期刊《德国应用化学》发表了这一成果。

研究小组报道了一个结晶诱导发光荧光团来定量地研究聚集蛋白的极性。这种溶剂变色探针，称为“AggRetina”探针，固有地与聚集的蛋白质结合，并表现出极性依赖的荧光发射波长漂移和黏度依赖的荧光强度增加。其极性灵敏度可以通过延长共轭长度来调节。通过这种探针，课题组研究人员观察到不同的蛋白质在聚集时具有不同的极性，从而导致不同的蛋白质水解抗性。

课题组人员进一步表明，极性主要在蛋白质错误折叠过程中降低，但粘度主要在不溶性聚集体形成时增加。最后，该课题组研究人员通过HaloTag生物正交标记对活性细胞中聚集蛋白的极性进行了量化，揭示了细胞聚集蛋白的极性不均一性。这项工作强调了错误折叠和聚集蛋白内部丰富的微环境细节，这些细节可能与它们的生化特性和致病性相关。

研究人员表示，蛋白质聚集间期的物理化学细节还很少被研究，特别是在活细胞中。

附：英文原文

Title: A Solvatochromic Fluorescent Probe Reveals Polarity Heterogeneity upon Protein Aggregation in Cells.

Author: Wang Wan, Lianggang Zeng, Wenhan Jin, Xinxin Chen, Di Shen, Yanan Huang, Mengdie Wang, Yulong Bai, Haochen Lyu, Xuepeng Dong, Zhenming Gao, Lei Wang, Xiaojing Liu, Yu Liu

Issue&Volume: 2021-09-25

Abstract: Physicochemical details at the interphase of protein aggregation have been less explored especially in live cells. Herein, we reported 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 polarity-dependent fluorescence emission wavelength shift and viscosity-dependent fluorescence intensity increase. Regulation of its polarity sensitivity was achieved by extending the conjugation length. Empowered by this probe, we observed that different proteins bear diverse polarity upon aggregation, leading to different resistance to proteolysis. We further showed that polarity primarily decreases during protein misfolding but viscosity mainly increases upon the formation of insoluble aggregates.  Finally, we quantified the polarity of aggregated protein-of-interest in live cells via HaloTag bioorthogonal labeling, revealing polarity heterogeneity within cellular aggregates. This work highlights the enriched micro-environment details inside misfolded and aggregated proteins that may correlate to their bio-chemical properties and pathogenicity.

DOI: 10.1002/anie.202107943

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202107943