A SERS-Active Electrospun Polymer Mesh for Spatially Localized pH Measurements of the Cellular Microenvironment

Extracellular pH (pHe) is an important chemical factor in many cellular processes and disease pathologies. The routine sampling of pHe in vitro could lead to innovative advances in therapeutics. To this end, we have fabricated a novel gold-coated polymer mesh, which facilitates the real-time measure...

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Bibliographic Details
Published in:Analytical chemistry (Washington) 2021-10, Vol.93 (41), p.13844-13851
Main Authors: Skinner, William H, Chung, Michael, Mitchell, Stephen, Akidil, Asli, Fabre, Kristin, Goodwin, Richard, Stokes, Adam A, Radacsi, Norbert, Campbell, Colin J
Format: Article
Language:English
Subjects:
Apoptosis
Cell death
Chemistry
Cytology
Electrospinning
Gold
Gold coatings
Medical innovations
Microenvironments
Morphology
Nanofibers
pH effects
Polymers
Polyurethane
Polyurethane resins
Raman spectra
Sensors
Staurosporine
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Summary:Extracellular pH (pHe) is an important chemical factor in many cellular processes and disease pathologies. The routine sampling of pHe in vitro could lead to innovative advances in therapeutics. To this end, we have fabricated a novel gold-coated polymer mesh, which facilitates the real-time measurement of pHe via surface-enhanced Raman scattering (SERS). In this proof of concept study, we apply our SERS sensor to measure metabolically induced changes in the pHe of carcinoma-derived cell line HepG2/C3A. We demonstrate that gold-coated polyurethane electrospun nanofibers (AuNF) have strong and reproducible SERS spectra of surface-adsorbed analytes. By functionalizing AuNF with pH-responsive reporter 4-mercaptobenzoic acid (MBA), we have developed an accurate pH SERS sensor for the extracellular microenvironment. We cultured HepG2/C3A on the surface of MBA-AuNF and measured an acidic shift in pHe at the cell–fiber interface. Following exposure to staurosporine, an apoptosis-inducing drug, we observed changes in the HepG2/C3A cellular morphology indicative of controlled cell death, and detected an increase in the pHe of HepG2/C3A. These results demonstrate how subtle changes in pHe, induced by the metabolic activity of cells, can be measured with our novel SERS sensor MBA-AuNF. The excellent pH measurement performance of MBA-AuNF provides a unique platform to study extracellular pH on the microscale and will help to deepen our understanding of pHe in disease pathology.
ISSN:0003-2700
1520-6882
DOI:10.1021/acs.analchem.1c02530