Programmable Deformation of DNA Nanostructures: Mastering Size and Topology for Tailored Mechanics

DNA nanostructures have emerged as versatile platforms for targeted drug delivery, high-sensitivity biosensing, and nanoscale computation. However, structural deformation and instability under environmental or mechanical stresses can compromise functionality, highlighting the need for rational design of their structures and properties. Here, we investigate the effects of size and topology on deformation mechanisms using coarse-grained molecular dynamics simulations. Our results reveal that size governs deformation through helical periodicity (∼10.5 bps/turn): when edge lengths deviate from integer helical turns (e.g., 15 bps), accumulated torsional stress destabilizes corners, whereas full-turn edges (e.g., 21 bps) maintain high structural symmetry. On the other hand, topology modulates the spatial distribution of flexibility along edges through the rigidity of the framework. Together, these results reveal a coupled size-topology mechanism: size primarily controls the magnitude of deformation and edge symmetry, while topology dictates how this strain manifests along the nanostructure, balancing global stability with local flexibility. This insight provides a framework for precisely controlling the mechanical behavior of DNA nanostructures and designing robust, programmable nanoscale materials for applications in drug delivery and biosensing.