alexa Deconvolution of complex G protein-coupled receptor signaling in live cells using dynamic mass redistribution measurements.

Journal of Bioengineering and Bioelectronics

Author(s): Schrder R, Janssen N, Schmidt J, Kebig A, Merten N,

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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. This article was published in Nat Biotechnol and referenced in Journal of Bioengineering and Bioelectronics

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