High-resolution label-free 3D mapping of extracellular pH of single living cells

Yanjun Zhang (), Yasufumi Takahashi, Sung Pil Hong, Fengjie Liu, Joanna Bednarska, Philip S. Goff, Pavel Novak, Andrew Shevchuk, Sahana Gopal, Iros Barozzi, Luca Magnani, Hideki Sakai, Yoshimoto Suguru, Takuto Fujii, Alexander Erofeev, Peter Gorelkin, Alexander Majouga, Dominik J. Weiss, Christopher Edwards, Aleksandar P. Ivanov, David Klenerman, Elena V. Sviderskaya (), Joshua B. Edel () and Yuri Korchev ()
Additional contact information
Yanjun Zhang: Imperial College London
Yasufumi Takahashi: Kanazawa University, Kakuma-machi
Sung Pil Hong: Imperial College London
Fengjie Liu: Department of Earth Science & Engineering, Imperial College London
Joanna Bednarska: Imperial College London
Philip S. Goff: St George’s, University of London
Pavel Novak: Imperial College London
Andrew Shevchuk: Imperial College London
Sahana Gopal: Imperial College London
Iros Barozzi: Imperial College London
Luca Magnani: Imperial College London
Hideki Sakai: University of Toyama
Yoshimoto Suguru: Kanazawa University, Kakuma-machi
Takuto Fujii: University of Toyama
Alexander Erofeev: National University of Science and Technology “MISIS”
Peter Gorelkin: National University of Science and Technology “MISIS”
Alexander Majouga: Lomonosov Moscow State University
Dominik J. Weiss: Department of Earth Science & Engineering, Imperial College London
Christopher Edwards: Imperial College London
Aleksandar P. Ivanov: Imperial College London
David Klenerman: University of Cambridge
Elena V. Sviderskaya: St George’s, University of London
Joshua B. Edel: Imperial College London
Yuri Korchev: Imperial College London

Nature Communications, 2019, vol. 10, issue 1, 1-9

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-13535-1

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