We have developed a simple assay to monitor the reduction, oxidation and isomerization of disulfide bonds in single proteins. Disulfide bond reactions are crucial to the function of one third of all proteins, yet these reactions remain poorly understood. We use proteins with engineered disulfide bonds to arrest the mechanical extension that occurs during mechanical unfolding (figure). Reduction of the disulfide bond after unfolding results into a further extension that is easily detectable with force spectroscopy. The reverse reaction (oxidative folding) is also easily studied by applying the force-quench protocol in the presence of a chaperone such as Protein Disulfide Isomerase (PDI). In collaboration with Dr. Brent Stockwell (Columbia) and Dr. Arne Holmgren (Karolinska) we are studying the role of PDI and Glutaredoxin in oxidative protein folding. We are also studying the regioselectivity and isomerization of disulfide bond reactions when there are two or more disulfide bonds within the same protein.