Sci. Adv. 3, e1602991 (2017)

Fluorescent labels are commonly used to study molecular interactions, but it is not clear if or how their use affects molecular dynamics. Feng Liang and co-workers from the Rowland Institute at Harvard University in the US and Swansea University in the UK have now investigated this question in a quantitative manner using a plasmonic antenna-in-a-nanocavity single-molecule biosensor to study DNA–protein dynamics. The team discovered that widely used fluorescent reporters such as fluorescein isothiocyanate (FITC) and green fluorescent protein (GFP) decrease the interaction between DNA and a protein called XPA by a factor of 3 and 18, respectively, due to weakened electrostatic interactions. The study concludes that traditional fluorescent labelling methods might thus be causing molecular interactions to be misestimated in many circumstances.