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. 2010 Sep;28(9):943-9.
doi: 10.1038/nbt.1671. Epub 2010 Aug 15.

Deconvolution of Complex G Protein-Coupled Receptor Signaling in Live Cells Using Dynamic Mass Redistribution Measurements

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Deconvolution of Complex G Protein-Coupled Receptor Signaling in Live Cells Using Dynamic Mass Redistribution Measurements

Ralf Schröder et al. Nat Biotechnol. .

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.

Comment in

  • A holistic view of GPCR signaling.
    Kenakin T. Kenakin T. Nat Biotechnol. 2010 Sep;28(9):928-9. doi: 10.1038/nbt0910-928. Nat Biotechnol. 2010. PMID: 20829829 No abstract available.

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