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P2008
Label-Free Optical Biosensor for Probing GPCR Ligand-Directed Functional Selectivity
Presenter Ann Ferrie, Corning Inc., USA
Additional Authors: Ye Fang
Realization of the complexity of G protein-coupled receptor (GPCR) signaling and ligand-directed functional selectivity demands high-resolution tools for studying GPCR behavior. Given its well-characterized agonist binding site and the availability of a wealth of structurally related ligands with functionally diverse properties, â2-adrenergic receptor (â2AR) has been used as an excellent model system for studying the mechanism of GPCR activation and signaling. Here we use non-invasive resonant waveguide grating (RWG) biosensor to systematically examine the kinetic profiles of human epidermoid carcinoma A431 cells in response to stimulation with a diverse array of â2AR ligands. The RWG biosensor offers an integrated signal, termed dynamic mass redistribution (DMR) signal, which closely reflects a global representation of GPCR signaling in native cells. Multi-parameter analysis of agonist-induced DMR signals indicates the presence of multiple ligand-specific states of the â2AR. The implications of DMR signals screening of biased ligands are discussed.