title: Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements.
abstract: Label-free biosensor technology based on dynamic mass redistribution (DMR) of cellular constituents promises to translate GPCR signaling into complex optical 'fingerprints' in real time in living cells. Here we present a strategy to map cellular mechanisms that define label-free responses, and we compare DMR technology with traditional second-messenger assays that are currently the state of the art in GPCR drug discovery. The holistic nature of DMR measurements enabled us to (i) probe GPCR functionality along all four G-protein signaling pathways, something presently beyond reach of most other assay platforms; (ii) dissect complex GPCR signaling patterns even in primary human cells with unprecedented accuracy; (iii) define heterotrimeric G proteins as triggers for the complex optical fingerprints; and (iv) disclose previously undetected features of GPCR behavior. Our results suggest that DMR technology will have a substantial impact on systems biology and systems pharmacology as well as for the discovery of drugs with novel mechanisms.
authors: Molecular, Cellular, and Pharmacobiology Section, Institute of Pharmaceutical Biology, University of Bonn, Bonn, Germany.
authors: Ralf
authors: R
authors: Schröder
authors: Nicole
authors: N
authors: Janssen
authors: Johannes
authors: J
authors: Schmidt
authors: Anna
authors: A
authors: Kebig
authors: Nicole
authors: N
authors: Merten
authors: Stephanie
authors: S
authors: Hennen
authors: Anke
authors: A
authors: Müller
authors: Stefanie
authors: S
authors: Blättermann
authors: Marion
authors: M
authors: Mohr-Andrä
authors: Sabine
authors: S
authors: Zahn
authors: Jörg
authors: J
authors: Wenzel
authors: Nicola J
authors: NJ
authors: Smith
authors: Jesús
authors: J
authors: Gomeza
authors: Christel
authors: C
authors: Drewke
authors: Graeme
authors: G
authors: Milligan
authors: Klaus
authors: K
authors: Mohr
authors: Evi
authors: E
authors: Kostenis
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015374:Biosensing Techniques / Q000379:methods*; D016466:CHO Cells; D002470:Cell Survival; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism; D009928:Organ Specificity; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043562:Receptors, G-Protein-Coupled; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D000262:Adenylyl Cyclases