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. IvanovDavid Klenerman, Elena V. Sviderskaya, Joshua B. Edel, Yuri Korchev

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

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.

Original languageEnglish
Article number5610
JournalNature Communications
Volume10
Issue number1
DOIs
StatePublished - 2019/12/01

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy

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