Ions as Architects of DNA Nanostructures: Mechanisms, Simulations, and Technological Frontiers

DNA, the most iconic molecular architecture, is not only the carrier of genetic information but also a programmable, biocompatible scaffold for nanoscale design. Its structural and physicochemical versatility makes it uniquely suited for self‐assembly, biomedical applications, and the development of dynamic devices and advanced materials. A key determinant of DNA behavior across organizational levels is its interaction with ions, which governs hydration, stability, and compaction from the molecular to the supramolecular scale. Beyond their biological roles, ion‐DNA interactions underpin a variety of technologies: in nanostructure assembly, cations stabilize DNA origami and multihelix constructs; in biosensing, ions enable aptamer folding, DNAzyme catalysis, and metal‐mediated base pairing; in nanomedicine, polyvalent cations drive DNA condensation into polyplexes for gene delivery and stabilize nanorobots for logic‐gated release; and in nanoelectronics and molecular computing, ions enhance DNA conductivity and act as molecular inputs in ion‐responsive logic gates. Ion‐induced condensation, a form of nanoscale confinement driven by electrostatics, remains a central phenomenon, linking biological function to material design. This review emphasizes the technological potential of ion‐driven DNA nanomechanics, integrating experimental evidence with multiscale modeling, and highlights the emerging predictive role of computational tools in guiding the design of next‐generation DNA‐based nanomaterials.