Journal
NATURE BIOTECHNOLOGY
Volume 28, Issue 9, Pages 943-950Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/nbt.1671
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Funding
- DFG (Deutsche Forschungsgemeinschaft) [KO 1582/3-1, MO 821/2-1, WE 4428/1-1, GRK 677]
- Dr. Hilmer Foundation
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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. (C) 2010 Nature America, Inc. All rights reserved.
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