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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Zhang, Yanjun 
Takahashi, Yasufumi  ORCID logo  https://orcid.org/0000-0003-2834-8300
Hong, Sung Pil 
Liu, Fengjie 
Bednarska, Joanna 

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.

Description

Keywords

Biophysics, Cell Line, Tumor, Diatoms, Humans, Hydrogen-Ion Concentration, Imaging, Three-Dimensional, Melanoma, Microscopy, Electron, Scanning, Neoplasms, Single-Cell Analysis

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC
Sponsorship
Engineering and Physical Sciences Research Council (EP/P012809/1)