Label-free optical biosensor for ligand-directed functional selectivity acting on β₂ adrenoceptor in living cells

Abstract 

Recent realization of ligand-directed functional selectivity demands high-resolution tools for studying receptor biology and ligand pharmacology. Here we use label-free optical biosensor to examine the dynamic mass redistribution of human epidermoid A431 cells in response to diverse β₂-adrenoceptor ligands. Multi-parameter analysis reveals distinct patterns in activation and signaling of the receptor induced by different agonists. Sequential and co-stimulation assays categorize various ligands for their ability to modulate signaling induced by catechol, a structural component of catecholamines. This study documents multiple ligand-specific states of the β₂-adrenoceptor and highlights the power of the biosensor assays for screening pathway-biased ligands.

Abbreviations: GPCR, G Protein-coupled receptor, β₂AR, β₂-Adrenoceptor, DMR, dynamic mass redistribution, RWG, resonant-waveguide grating, cAMP, cyclic adenosine monophosphate, DIPC, dynamin inhibitory peptide, SPR, surface plasmon resonance, PWR, plasmon-waveguide resonance

Keywords: Optical biosensor, G protein-coupled receptor, β₂-adrenoceptor, Ligand-directed functional selectivity