Signal transduction profiling using label-free biosensors.
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 Ca(2+), 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.
Cooper
Matthew A
MA
Institute for Molecular Bioscience, The University of Queensland, St Lucia, Queensland, Australia. m.cooper@uq.edu.au
D000818:Animals; D015374:Biosensing Techniques; D006801:Humans; D017382:Reactive Oxygen Species / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D020349:Surface Plasmon Resonance / Q000379:methods*
D017382:Reactive Oxygen Species; D043562:Receptors, G-Protein-Coupled