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Mol Imaging Biol. 2019 Apr 11. doi: 10.1007/s11307-019-01335-4. [Epub ahead of print]

Mapping pH at Cancer Cell Surfaces.

Author information

1
Physics Department, University of Rhode Island, 2 Lippitt Rd, Kingston, RI, 02874, USA.
2
Department of Molecular Biophysics and Biochemistry, Yale, Box 208114, New Haven, CT, 06520-8114, USA.
3
Physics Department, University of Rhode Island, 2 Lippitt Rd, Kingston, RI, 02874, USA. andreev@uri.edu.

Abstract

PURPOSE:

To develop a tool to measure the pH at the surfaces of individual cells.

PROCEDURES:

The SNARF pH-sensitive dye was conjugated to a pHLIP® peptide (pH-Low Insertion Peptide) that binds cellular membranes in tumor spheroids. A beam splitter allows simultaneous recording of two images (580 and 640 nm) by a CCD camera. The ratio of the two images is converted into a pH map resolving single spheroid cells. An average pH for each cell is calculated and a pH histogram is derived.

RESULTS:

Surface pH depends on cellular glycolytic activity, which was varied by adding glucose or deoxy-glucose. Glucose was found to decrease the surface pH relative to the pH of the bulk solution. The surface pH of metastatic cancer cells was lower than that of non-metastatic cells indicating a higher glycolytic activity.

CONCLUSIONS:

Our method allows cell surface pH measurement and its correlation with cellular glycolytic activity.

KEYWORDS:

SNARF fluorescence; Tumor acidity; Warburg effect; pH measurements; pHLIP

PMID:
30989440
DOI:
10.1007/s11307-019-01335-4

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