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

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...

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Bibliographic Details
Published in:Nature communications Vol. 10; no. 1; pp. 5610 - 9
Main Authors: Zhang, Yanjun, Takahashi, Yasufumi, Hong, Sung Pil, Liu, Fengjie, Bednarska, Joanna, Goff, Philip S., Novak, Pavel, Shevchuk, Andrew, Gopal, Sahana, Barozzi, Iros, Magnani, Luca, Sakai, Hideki, Suguru, Yoshimoto, Fujii, Takuto, Erofeev, Alexander, Gorelkin, Peter, Majouga, Alexander, Weiss, Dominik J., Edwards, Christopher, Ivanov, Aleksandar P., Klenerman, David, Sviderskaya, Elena V., Edel, Joshua B., Korchev, Yuri
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 06.12.2019
Nature Publishing Group
Nature Portfolio
Subjects:
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14
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631/57/2265
631/57/2282
639/638
639/925
Barrel plating
Biophysics
Breast cancer
Cancer
Cell Line, Tumor
Conductance
Diatoms - cytology
Heterogeneity
Humanities and Social Sciences
Humans
Hydrogen-Ion Concentration
Imaging, Three-Dimensional - methods
Mapping
Melanoma
Microscopy, Electron, Scanning
multidisciplinary
Neoplasms - diagnostic imaging
Neoplasms - pathology
pH effects
Response time
Science
Science (multidisciplinary)
Sensitivity
Single-Cell Analysis - methods
Spatial resolution
Temporal resolution
Tumors
ISSN:2041-1723, 2041-1723
Online Access:Get full text
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Summary: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. Current methods to measure extracellular pH are often limited in resolution and response times. Here the authors present a label-free nanoprobe, consisting of a zwitterionic nanomembrane at the tip of a nanopipette, which enables high spatiotemporal resolution pH measurements and topography-pH 3D mapping in live cancer cells.
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ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-019-13535-1