Topology-Dependent Dissociation Kinetics in DNA Tetrahedron Assemblies.

Abstract

DNA tetrahedra are versatile programmable nanostructures that can assemble into higher-order architectures through sticky-end hybridization. Here, we use coarse-grained molecular dynamics simulations with the oxDNA model to examine dissociation of hybridized sticky-end linkers in finite linear (1D), looped (2D), and multiply connected (3D) tetrahedron assemblies containing 4-9-bp linkers at 300-330 K. Increasing sticky-end length systematically stabilized linker hybridization, increased hydrogen-bond occupancy, and generally increased the effective activation energy for dissociation. Increasing connectivity suppressed global configurational fluctuations but did not monotonically delay the first linker-opening event. Comparative simulations of isolated hybridized duplexes further showed that incorporation into tetrahedral frameworks shifts opening times and effective activation energies in a topology- and linker-length-dependent manner. In particular, the 3D assemblies displayed sequential opening times with the greatest temporal separation between early and late dissociation events, indicating that the kinetic environment of the remaining linkers evolves as connectivity is progressively lost. Overall, the results demonstrate that network topology regulates linker dissociation through an interplay between local hybridization energetics, configurational constraints, and topology-dependent structural reorganization rather than through simple monotonic stabilization with increasing connectivity.