Dynamic DNA Origami Device for Measuring Compressive Depletion Forces

The ability to self-assemble nanodevices with programmed structural dynamics that can sense and respond to the local environment could enable transformative applications in fields including molecular robotics, nanomanufacturing, and nanomedicine. The responsive function of biomolecules is often driven by alterations in conformational distributions mediated by highly sensitive interactions with the local environment. Here, we mimic this approach by engineering inherent nanoscale structural dynamics (nanodynamics) into a DNA device that exhibits a distribution of conformations including two stable states separated by a transition state where the energy barrier height is on the scale of the thermal energy, kBT = 4.1 pN·nm, enabling spontaneous transitions between states. We further establish design principles to regulate the equilibrium and kinetic behavior by substituting a few DNA strand components. We use single-molecule Förster resonance energy transfer measurements to show these nanodynamic properties are sensitive to sub-piconewton depletion forces in the presence of molecular crowding agents, and the device can measure depletion forces with a resolution of ∼100 fN. We anticipate that this approach of engineering nanodynamic DNA devices will enable molecular-scale systems that sense and respond to their local environment with extremely high sensitivity.