Single-fluorophore biosensors for sensitive and multiplexed detection of signalling activities

Sohum Mehta, Yong Zhang, Richard H. Roth, Jin fan Zhang, Albert Mo, Brian Tenner, Richard L. Huganir, Jin Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Unravelling the dynamic molecular interplay behind complex physiological processes such as neuronal plasticity requires the ability to both detect minute changes in biochemical states in response to physiological signals and track multiple signalling activities simultaneously. Fluorescent protein-based biosensors have enabled the real-time monitoring of dynamic signalling processes within the native context of living cells, yet most commonly used biosensors exhibit poor sensitivity (for example, due to low dynamic range) and are limited to imaging signalling activities in isolation. Here, we address this challenge by developing a suite of excitation ratiometric kinase activity biosensors that offer the highest reported dynamic range and enable the detection of subtle changes in signalling activity that could not be reliably detected previously, as well as a suite of single-fluorophore biosensors that enable the simultaneous tracking of as many as six distinct signalling activities in single living cells.

Original languageEnglish (US)
Pages (from-to)1215-1225
Number of pages11
JournalNature cell biology
Volume20
Issue number10
DOIs
StatePublished - Oct 1 2018

ASJC Scopus subject areas

  • Cell Biology

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