Single molecule mechanical techniques like AFM or optical tweezers provide insight into the conformational dynamics of macromolecules and allow reconstructing details of the free energy landscapes that direct such processes.1 Single-molecule mechanical assays have been successfully applied to analyze large conformational changes like the ones that occur in protein unfolding or in the motion of molecular motors. However, conformational transitions in many native proteins involve much smaller length changes, on the order of a nanometer or less.2 Conventional force spectroscopy at such fine resolution is affected by significant signal-to-noise limitations in the regime of low forces (less than 10 pN). Yet it is precisely the regime of low forces that deserves attention, because the functionally relevant conformational dynamics of proteins and other biological macromolecules are located here.