Heavy metals like cadmium and mercury are "invisible" poisons that can accumulate and disrupt both metabolic and endocrine homeostasis of humans and livestock. While traditional analytical methods allow for highly accurate measurements of these metal concentrations, they commonly do not allow for time-dependent or location-specific in vivo measurements. As the uptake and distribution of this extremely toxic metal are not yet understood, highly sensitive and non-invasive methods are needed for its detection in a living organism. With the introduction of a cysteine residue at position 205, Chapleau and colleagues from the University of California, illustrate in Protein Science how the green fluorescent protein (GFP) from Aequorea victoria was converted into a highly specific biosensor for mercury:
- the mutant protein exhibits a dramatic absorbance and fluorescence change upon mercuration at neutral pH also in presence of metal binding agents like EDTA;
- these changes exhibit sigmoidal binding behavior with respect to the metal concentration with a detection limit in the low nanomolar range;
- time-resolved binding studies indicate rapid subsecond binding of the metal to protein;
- crystal structure and mass spectrometry further characterize this novel biosensor.
The aim of the authors is to provide a biosensor that, in presence of mercury, decrease (or anyway changes) its own fluorescence. Although (until now) the only "in vivo" application claimed in the title is the "GFP"-sensor expression in bacteria challenged with mercury 20 micromolar, the use of GFP as a mercury-specific noninvasive biosensor is a first example of a real-time biosensor that would enable the direct imaging of the uptake of heavy metals by a living cell, or (better) a living animal.
Chapleau, R.R., Blomberg, R., Ford, P.C., Sagermann, M. (2008). Design of a highly specific and noninvasive biosensor suitable for real-time in vivo imaging of mercury (II) uptake. Protein Science DOI: 10.1110/ps.073358908