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Research Article

Signal transduction profiling using label-free biosensors

Pages 224-233 | Published online: 02 Jul 2009
 

Abstract

Knowledge of the way in which ligands modulate cellular responses via membrane-associated receptors is of central importance to drug discovery and elucidation of signal transduction pathways. Biophysical label-free methods can be used to characterize ligand and drug candidate interactions with neurotransmitters, cytokine receptors, tyrosine kinase receptors, ligand- and voltage-gated ion channels, G protein-coupled receptors (GPCRs), and antibody receptors. Ligand or drug candidate screening typically involves selecting ligands or subsets of a compound library for analysis, transfecting a cell line overexpressing the target receptor, then monitoring one or two downstream reporters of receptor activation such as Ca2+, cAMP, inositol phosphate, etc. Inevitably, this process leads to a data set predicated by these selections. In contrast, label-free screening techniques allow a holistic, pathway-independent screening strategy to provide a functional or phenotypic readout of receptor activation. Detection techniques that measure changes in cell conductance, viscoelastic properties, refractive index, and other optical parameters that are modulated as a consequence of receptor activation are reviewed.

Acknowledgments

Declaration of interest: The author reports no conflicts of interest.

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