Painting protein misfolding in the cell in real time with an atomic-scale brush.

The direct observation of specific biochemical events in living cells is now possible as a result of combined advances in molecular biology and fluorescence microscopy. By genetically encoding the source of a unique spectroscopic signal, target proteins can be selectively detected within the complex cellular environment, with limited interference from background signals. A recent study takes advantage of arsenical reagent-based methodologies to monitor in vivo protein misfolding and inclusion body formation in real time. This approach promises to yield important information on the kinetics of aggregate formation in living cells and its relation to the time-course of protein expression and post-translational processing. The ability to follow protein self-association in real time accurately from its early stages is unique to this method, and has far-reaching implications for both biotechnology and misfolding-based disease.