Framework Nucleic Acid-Mediated DNAzyme Chaperoning for Sensitive Trace Metal Ion Mapping on Live Neuronal Cell Membranes
Tianqi Xu
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorFan Li
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorYichao Jin
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorFeng Jia
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorYu Wang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorTao Lv
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorYueyue Zhang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorMin Li
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorChunhai Fan
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
Search for more papers by this authorCorresponding Author
Mingqiang Li
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiaohua Zhang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Shaopeng Wang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiaolei Zuo
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorTianqi Xu
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorFan Li
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorYichao Jin
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorFeng Jia
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
These authors contributed equally to this work.
Search for more papers by this authorYu Wang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorTao Lv
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorYueyue Zhang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorMin Li
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
Search for more papers by this authorChunhai Fan
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
Search for more papers by this authorCorresponding Author
Mingqiang Li
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiaohua Zhang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Shaopeng Wang
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorCorresponding Author
Xiaolei Zuo
Institute of Molecular Medicine, Shanghai Key Laboratory for Nucleic Acid Chemistry and Nanomedicine, Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127 China
State Key Laboratory of Synergistic Chem-Bio Synthesis, School of Chemistry and Chemical Engineering, New Cornerstone Science Laboratory, Frontiers Science Center for Transformative Molecules, Zhangjiang Institute for Advanced Study and National Center for Translational Medicine, Shanghai Jiao Tong University, Shanghai, 200240 China
E-mail: [email protected]; [email protected]; [email protected]; [email protected]
Search for more papers by this authorGraphical Abstract
Inspired by the beneficial effects of molecular chaperones on the stability and functionality of proteins, we present in this study the development of tetrahedral DNA frameworks (TDF) as chaperones for DNAzymes. Integration of TDF with DNAzymes significantly improves sensitivity and stability, facilitating precise and quantitative mapping of local trace metal ion concentrations on live neuronal cell membranes. This adaptable approach sets a foundation for developing sensitive nanodevices based on DNAzymes.
Abstract
The transient release of metal ions at neuronal cell membranes holds significant implications in neurophysiology and pathology. Consequently, there is a pressing need for sensitive methodologies capable of quantitatively mapping local metal ion concentrations in live cells, aiming to unravel potential mechanisms underlying neurological disorders. DNAzymes have emerged as versatile tools for metal ion detection in live cells, owing to their specificity and other inherent advantages. Efforts to broaden their utility have focused on enhancing the stability and sensitivity of DNAzymes. Inspired by the beneficial effects of molecular chaperones on the stability and functionality of proteins, we present in this study the development of tetrahedral DNA frameworks (TDF) as chaperones for DNAzymes, aiming at enhancing the stability and activity of DNAzymes. Integration of TDF with DNAzymes is shown to significantly enhance metal ion detection performance, resulting in elevated stability and a two-fold increase in sensitivity, attributed to alterations in the local net charge induced by TDF. In vitro investigations demonstrate that the nanodevice developed here faithfully maps Cu2+ concentrations within a range of 0–10 µM on the membrane of neuronal cells, meeting the requirements for Cu2+ sensing under both physiological and pathological conditions. This work presents an easily adaptable approach to enhance the performance of DNAzymes and lays the foundations for the development of other DNAzyme-based sensitive detection nanodevices.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the supplementary material of this article.
Supporting Information
| Filename | Description |
|---|---|
| anie202506640-sup-0001-SuppMat.docx4.5 MB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1K. Vogt, J. Mellor, G. Tong, R. Nicoll, Neuron 2000, 26, 187–196.
- 2S. C. Dodani, A. Firl, J. Chan, C. I. Nam, A. T. Aron, C. S. Onak, K. M. Ramos-Torres, J. Paek, C. M. Webster, M. B. Feller, C. J. Chang, Proceedings of the National Academy of Sciences, USA 2014, 111, 16280–16285.
- 3S. L. Sensi, P. Paoletti, A. I. Bush, I. Sekler, Nat. Rev. Neurosci. 2009, 10, 780–791.
- 4S. G. Kaler, Nat. Rev. Neurol. 2011, 7, 15–29.
- 5M. Kawahara, K. I. Tanaka, M. Kato-Negishi, Journal of Clinical Biochemistry and Nutrition 2022, 71, 7–15.
- 6Z. Xu, J. Zhou, BioMetals 2013, 26, 863–878.
- 7L. P. Savtchenko, M. M. Poo, D. A. Rusakov, Nat. Rev. Neurosci. 2017, 18, 598–612.
- 8W. Zhou, R. Saran, J. Liu, Chem. Rev. 2017, 117, 8272–8325.
- 9M. Liu, D. Chang, Y. Li, Acc. Chem. Res. 2017, 50, 2273–2283.
- 10E. M. McConnell, I. Cozma, Q. Mou, J. D. Brennan, Y. Lu, Y. Li, Chem. Soc. Rev. 2021, 50, 8954–8994.
- 11R. C. Qian, Z. R. Zhou, W. Guo, Y. Wu, Z. Yang, Y. Lu, J. Am. Chem. Soc. 2021, 143, 5737–5744.
- 12R. C. Qian, Z. R. Zhou, Y. Wu, Z. Yang, W. Guo, D. W. Li, Y. Lu, Angew Chem Int Ed 2022, 61, e202210935.
- 13D. Yi, H. Zhao, J. Zhao, L. Li, J. Am. Chem. Soc. 2023, 145, 1678–1685.
- 14J. Zhao, Z. Li, Y. Shao, W. Hu, L. Li, Angew Chem Int Ed 2021, 60, 17937–17941.
- 15Z. Yang, K. Y. Loh, Y. T. Chu, R. Feng, N. S. R. Satyavolu, M. Xiong, S. M. Nakamata Huynh, K. Hwang, L. Li, H. Xing, X. Zhang, Y. R. Chemla, M. Gruebele, Y. Lu, J. Am. Chem. Soc. 2018, 140, 17656–17665.
- 16P. Wu, K. Hwang, T. Lan, Y. Lu, J. Am. Chem. Soc. 2013, 135, 5254–5257.
- 17A. R. Chandrasekaran, Nat. Rev. Chem. 2021, 5, 225–239.
- 18S. Omkar, A. Rysbayeva, A. W. Truman, Trends Biochem. Sci. 2023, 48, 662–664.
- 19H. Saibil, Nat. Rev. Mol. Cell Biol. 2013, 14, 630–642.
- 20L. A. Parra, T. B. Baust, A. D. Smith, J. D. Jaumotte, M. J. Zigmond, S. Torres, R. K. Leak, J. A. Pino, G. E. Torres, J. Biol. Chem. 2016, 291, 17510–17522.
- 21A. Groth, A. Corpet, A. J. L. Cook, D. Roche, J. Bartek, J. Lukas, G. Almouzni, Science 2007, 318, 1928–1931.
- 22M. J. Thiele, M. D. Davari, M. König, I. Hofmann, N. O. Junker, T. Mirzaei Garakani, L. Vojcic, J. Fitter, U. Schwaneberg ACS Catalysis 8, 10876–10887.
- 23J. Wang, H. Zhang, D. Yin, X. Xu, T. Tan, Y. Lv, Synth Syst Biotechnol 2021, 6, 163–172.
- 24Z. Ge, H. Gu, Q. Li, C. Fan, J. Am. Chem. Soc. 2018, 140, 17808–17819.
- 25T. Zhang, T. Tian, Y. Lin, Adv. Mater. 2022, 34, 2107820.
- 26J. Liu, X. Jing, M. Liu, F. Li, M. Li, Q. Li, J. Shi, J. Li, L. Wang, X. Mao, Sci. Rob. 2022, 7, eabq5151.
- 27J. Fu, Y. R. Yang, A. Johnson-Buck, M. Liu, Y. Liu, N. G. Walter, N. W. Woodbury, H. Yan, Nat. Nanotechnol. 2014, 9, 531–536.
- 28P. Song, J. Shen, D. Ye, B. Dong, F. Wang, H. Pei, J. Wang, J. Shi, L. Wang, W. Xue, Nat. Commun. 2020, 11, 838.
- 29H. Zhao, M. Li, S. Lu, N. Cao, X. Zuo, S. Wang, M. Li, Analyst 2023, 148, 906–911.
- 30F. Yin, M. Li, X. Mao, F. Li, X. Xiang, Q. Li, L. Wang, X. Zuo, C. Fan, Y. Zhu, Angew Chem Int Ed 2020, 132, 10492–10496.
- 31M. Li, H. Ding, M. Lin, F. Yin, L. Song, X. Mao, F. Li, Z. Ge, L. Wang, X. Zuo, J. Am. Chem. Soc. 2019, 141, 18910–18915.
- 32Y. Zhou, Q. Yang, F. Wang, Z. Zhou, J. Xu, S. Cheng, Y. Cheng, Int. J. Nanomed. 16, 2021, 1805–1817.
- 33D. Zhu, J. Huang, Y. Xia, S. Su, X. Zuo, Q. Li, L. Wang, Chemosensors 2023, 11, 358.
- 34J. Liu, Y. Lu, J. Am. Chem. Soc. 2007, 129, 9838–9839.
- 35H. Gu, K. Furukawa, Z. Weinberg, D. F. Berenson, R. R. Breaker, J. Am. Chem. Soc. 2013, 135, 9121–9129.
- 36P. M. Roos, O. Vesterberg, T. Syversen, T. P. Flaten, M. Nordberg, Biol. Trace Elem. Res. 2013, 151, 159–170.
- 37A. Hopt, S. Korte, H. Fink, U. Panne, R. Niessner, R. Jahn, H. Kretzschmar, J. Herms, J. Neurosci. Methods 2003, 128, 159–172.
- 38M. Kawahara, K.-i. Tanaka, M. Kato-Negishi, Int. J. Mol. Sci. 2021, 22, 7242.
