Some biomolecules are able to generate directional forces by rectifying random thermal motions. This allows these molecular machines to perform mechanical tasks such as intracellular cargo transport or muscle contraction1 in plants and animals. Although some artificial molecular machines have been synthesized2, 3, 4 and used collectively to perform mechanical tasks5, 6, 7, so far there have been no direct measurements of mechanical processes at the single-molecule level. Here we report measurements of the mechanical work performed by a synthetic molecule less than 5 nm long. We show that biased Brownian motion of the sub-molecular components in a hydrogen-bonded rotaxane8—a molecular ring threaded onto a molecular axle—can be harnessed to generate significant directional forces. We used the cantilever of an atomic force microscope to apply a mechanical load to the ring during single-molecule pulling–relaxing cycles. The ring was pulled along the axle, away from the thermodynamically favoured binding site, and was then found to travel back to this site against an external load of 30 pN. Using fluctuation theorems, we were able to relate measurements of the work done at the level of individual rotaxane molecules to the free-energy change as previously determined from ensemble measurements. The results show that individual rotaxanes can generate directional forces of similar magnitude to those generated by natural molecular machines.
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