DNA Origami Nanomechanical Amplifiers for Resolving Single-Molecule Binding Events

<jats:p>Mechanical amplification of minute length changes enables precise measurements across many orders of magnitude, from macroscopic metrology to optical instrumentation. Extending this principle to molecular systems could provide a route to monitoring nanoscale structural changes without relying on analyte labeling or fluorescence-based distance measurements. Here we present a DNA origami nanomechanical amplifier that converts sub-nanometre-scale molecular conformational changes into amplified mechanical displacements that can be tracked in real time at the single-molecule level. The platform resolves geometric changes associated with DNA hybridization, secondary-structure formation, DNA strand-exchange dynamics, and ligand-induced aptamer folding, enabling quantitative analysis of molecular kinetics and direct observation of transient intermediates and heterogeneous conformational ensembles. By translating molecular recognition events into mechanically amplified signals, our approach establishes a general framework for monitoring binding-coupled conformational dynamics and extends the scope of single-molecule measurements beyond conventional optical readouts.</jats:p>