DNA as a model in polymer mechanochemistry

Mechanical forces shape the behavior of materials across all scales, from geological processes to molecular reactions. In polymers, such forces can activate specific chemical bonds, which forms the principle of the field of polymer mechanochemistry. This discipline seeks to harness mechanical energy to drive selective reactions along polymer backbones. Yet, despite major progress, the field remains limited by the synthetic complexity of mechanophores and by analytical tools that cannot resolve bond scission with molecular precision. DNA provides an exceptional alternative to conventional polymers. Its monodispersity, sequence control, and structural programmability make it a uniquely tunable material for studying force–reactivity relationships. Furthermore, next-generation sequencing (NGS) enables single-nucleotide resolution of fragmentation events, which transforms DNA into a quantitative probe for mechanochemical reactions. This thesis investigates where mechanochemical activation occurs within macromolecules and how specific structural features influence the localization of force-induced reactivity. Here we show that DNA can be engineered as a programmable mechanochemical platform in which structural motifs, such as nicks (single-strand breaks in the backbone) and hairpins, act as intrinsic mechanophore analogs that focus and direct mechanical stress. Under ultrasound and freeze–thaw activation, these motifs guide bond rupture to predetermined sites, as verified by NGS and supported by molecular dynamics simulations. Our findings reveal that DNA’s stiff, highly programmable structure can be exploited to tune the precision and spatial localization of mechanochemical scission far beyond what is achievable with synthetic polymers. A single nick provides a weak point for site-selective activation, while hairpins enable enhanced control through geometric force focusing. Extending the concept to freezing-induced stress uncovers a new mechanochemical regime relevant to cryopreservation, where ice formation exerts sufficient tension to cleave DNA covalent bonds. Together, these results establish DNA as a model system for decoding how molecular structure governs mechanical reactivity, laying the foundation for the rational design of responsive materials and molecular devices that translate mechanical energy into precise chemical transformations.