An Entropic Force Microscope Enables Nano-Scale Conformational Probing of Biomolecules

Entropy is fundamentally important in nearly all physical phenomena, but nature’s exquisite control over the underlying randomness masks a complexity that has proven challenging to synthetically replicate. Here we show how the inherently disordered dynamics governing macromolecular transport in confined surroundings, conventionally suppressed as an undesirable noisy background, can paradoxically be precisely controlled. This ability lays a foundation for an entropic force microscope, a sensitive probe of nanoscale biomolecular conformation capable of resolving previously unseen details about DNA-protein binding interactions at size scales below the limits of conventional techniques.