Abstract
The formation of higher-order structures in natural biopolymers like polypeptides and nucleic acids is governed by sequence specificity and monomer chemistry. Nucleic acids can assemble into programmable nanostructures through base-pairing interactions, but their chemical diversity is limited to four nucleobases. DNA amphiphiles address this by introducing orthogonal interactions through non-nucleosidic modifications. These amphiphiles self-assemble into diverse morphologies, such as spheres, fibers, or nanosheets, with closely packed, parallel DNA strands on their exterior. This unusual arrangement creates emergent properties absent in simple DNA strands. Here, we show that the precise sequence of single-stranded DNA, independent of base-pairing, can program the self-assembled morphology of DNA amphiphiles. Remarkably, small sequence variations induce the formation of non-equilibrium DNA nanotoroids, rather than conventional morphologies. The nanotoroids form as on-pathway structures via a competitive mechanism, only when a toroid-selective DNA sequence is used. They can be stabilized non-covalently by a small molecule cross-linker or co-assembly with a secondary DNA amphiphile. Molecular dynamics demonstrated the dependence of toroid formation on the structure of the end-p stacking unit. This work introduces a new class of DNA-based nanotoroid materials with assembly properties controlled by unique sequences, akin to proteins, for applications in cell delivery, nano-filtration, nanoreactors, and materials templation.
