Hierarchical Reinforcement of Wireframe DNA Origami Nanotubes: Effects of Molecular Connectivity, Edge Architecture, Geometry, and Bracing on Tensile Mechanics

Abstract The mechanical performance of wireframe DNA origami nanotubes is governed by a complex interplay between molecular connectivity, edge architecture, geometry, and network topology. In this study, coarse-grained molecular dynamics simulations using the oxDNA2 model were employed to systematically investigate hierarchical reinforcement mechanisms in wireframe DNA origami nanotubes through variations in molecular connectivity, edge design, cross-sectional geometry, nanotube length, and internal bracing. Mechanical loading was applied using steered molecular dynamics tensile-pulling protocols, and force–strain responses were analyzed together with hydrogen-bond evolution and structural deformation pathways. Triplicate simulations of the principal nanotube architectures were used to characterize the variability of the mechanical response. The reference triangular nanotube exhibited markedly different behavior depending on molecular connectivity. Unligated structures underwent localized postyield failure, with tensile tearing preferentially initiating at scaffold double-crossover regions, and progressive loss of force-transmission capability despite retaining a substantial fraction of their hydrogen bonds. In contrast, ligated nanotubes maintained mechanical coherence throughout extensive dehybridization and consistently reached a backbone-dominated stretching regime. Increasing nanotube length reduced the effective stiffness of the overall structure while leaving the intrinsic tensile stretch modulus largely unchanged. Replacing double-crossover (DX) edges with six-helix-bundle (6HB) edges substantially increased both stretch modulus and yield force, highlighting the importance of edge rigidity in determining tensile performance. Modifying the cross-section from triangular to square improved load sharing through the introduction of additional longitudinal load-bearing members, while diagonal bracing modified load sharing and network-level stress redistribution, with effects dependent on molecular connectivity. Collectively, the results reveal a hierarchy of reinforcement mechanisms operating across multiple structural levels. Molecular connectivity governs force transmission, edge architecture controls local rigidity, geometry regulates load sharing, and bracing enhances network connectivity and stress redistribution. These findings establish design principles for the rational engineering of mechanically robust wireframe DNA origami nanostructures and provide guidance for the development of load-bearing DNA-based nanodevices.