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TitleLabel-free visualization and quantification of single cell signaling activity using metal-clad waveguide (MCWG)-based microscopy.
Publication TypeJournal Article
Year of Publication2018
AuthorsSöllradl, Thomas, Frederic A. Banville, Ulrike Fröhlich, Michael Canva, Paul G. Charette, and Michel Grandbois
JournalBiosens Bioelectron
Date Published2018 Feb 15
KeywordsApoptosis, Biosensing Techniques, Cell Line, Endothelial Cells, Equipment Design, Humans, Microscopy, Optical Imaging, Signal Transduction, Single-Cell Analysis, TNF-Related Apoptosis-Inducing Ligand

Label-free biosensing methods are very effective for studying cell signaling cascade activation induced by external stimuli. Assays generally involve a large number of cells and rely on the underlying assumption that cell response is homogeneous within a cell population. However, there is an increasing body of evidence showing that cell behavior may vary significantly even among genetically identical cells. In this paper, we demonstrate the use of metal-clad waveguide (MCWG)-based microscopy for label-free real-time monitoring of signaling activity and morphology changes in a small population of cells, with the ability to resolve individual cells. We demonstrate the potential of this approach by quantifying apoptosis-induced intracellular activity in individual cells following exposure to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and by visualizing and quantifying extracellular changes in endothelial cell layer integrity following the activation of the proteinase-activated receptor 1 (PAR1) by thrombin. Results show that averaged signals obtained from a cell population may incorrectly reflect the actual distribution of morphology and kinetics parameters across a cell population by a significant margin.

Alternate JournalBiosens Bioelectron
PubMed ID28957707