Abstract

Dynamic mapping of extracellular pH (pHe) at the single-cell level is critical for understanding the role of H+ in cellular and subcellular processes, with particular importance in cancer. While several pHe sensing techniques have been developed, accessing this information at the single-cell level requires improvement in sensitivity, spatial and temporal resolution. We report on a zwitterionic label-free pH nanoprobe that addresses these long-standing challenges. The probe has a sensitivity > 0.01 units, 2 ms response time, and 50 nm spatial resolution. The platform was integrated into a double-barrel nanoprobe combining pH sensing with feedback-controlled distance dependance via Scanning Ion Conductance Microscopy. This allows for the simultaneous 3D topographical imaging and pHe monitoring of living cancer cells. These classes of nanoprobes were used for real-time high spatiotemporal resolution pHe mapping at the subcellular level and revealed tumour heterogeneity of the peri-cellular environments of melanoma and breast cancer cells.

Details

Title
High-resolution label-free 3D mapping of extracellular pH of single living cells
Author
Zhang, Yanjun 1 ; Takahashi, Yasufumi 2   VIAFID ORCID Logo  ; Hong, Sung Pil 3 ; Liu, Fengjie 4 ; Bednarska, Joanna 5 ; Goff, Philip S 6   VIAFID ORCID Logo  ; Novak, Pavel 7 ; Shevchuk, Andrew 5 ; Gopal, Sahana 5 ; Barozzi, Iros 3 ; Magnani, Luca 3   VIAFID ORCID Logo  ; Sakai, Hideki 8 ; Yoshimoto Suguru 9 ; Fujii, Takuto 8 ; Erofeev, Alexander 10 ; Gorelkin, Peter 11 ; Majouga, Alexander 12 ; Weiss, Dominik J 4 ; Edwards, Christopher 5 ; Ivanov, Aleksandar P 13   VIAFID ORCID Logo  ; Klenerman, David 14 ; Sviderskaya, Elena V 6   VIAFID ORCID Logo  ; Edel, Joshua B 13   VIAFID ORCID Logo  ; Korchev, Yuri 15 

1  Department of Medicine, Imperial College London, London, UK; Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China 
2  Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan; Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Agency (JST), Saitama, Japan 
3  Department of Surgery and Cancer, Imperial College London, London, UK 
4  Department of Earth Science & Engineering, Imperial College London, London, UK 
5  Department of Medicine, Imperial College London, London, UK 
6  Cell Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s, University of London, London, UK 
7  Department of Medicine, Imperial College London, London, UK; National University of Science and Technology “MISIS”, Moscow, Russian Federation 
8  Department of Pharmaceutical Physiology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan 
9  Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan 
10  National University of Science and Technology “MISIS”, Moscow, Russian Federation; Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation 
11  National University of Science and Technology “MISIS”, Moscow, Russian Federation 
12  Department of Chemistry, Lomonosov Moscow State University, Moscow, Russian Federation 
13  Department of Chemistry, Imperial College London, London, UK 
14  Department of Chemistry, University of Cambridge, London, UK 
15  Department of Medicine, Imperial College London, London, UK; Nano Life Science Institute (WPI-NanoLSI), Kanazawa University, Kakuma-machi, Kanazawa, Japan 
Pages
1-9
Publication year
2019
Publication date
Dec 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-13535-1
ProQuest document ID
2322188055
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.