Knots are some of the most remarkable topological features in nature. Self-assembly of knotted polymers without breaking or forming covalent bonds is challenging, as the chain needs to be threaded through previously formed loops in an exactly defined order. Here we describe principles to guide the folding of highly knotted single-chain DNA nanostructures as demonstrated on a nano-sized square pyramid. Folding of knots is encoded by the arrangement of modules of different stability based on derived topological and kinetic rules. Among DNA designs composed of the same modules and encoding the same topology, only the one with the folding pathway designed according to the "free-end" rule folds efficiently into the target structure. Besides high folding yield on slow annealing, this design also folds rapidly on temperature quenching and dilution from chemical denaturant. This strategy could be used to design folding of other knotted programmable polymers such as RNA or proteins.
COBISS.SI-ID: 5880858
Polypeptides and polynucleotides are programmable natural polymers whose linear sequence can be easily designed and synthesized by the cellular transcription/translation machinery. Nature primarily uses proteins as the molecular machines and nucleic acids as the medium for the manipulation of heritable information. A protein's tertiary structure and function is defined by multiple cooperative weak long-range interactions that have been optimized through evolution. DNA nanotechnology uses orthogonal pairwise interacting modules of complementary nucleic acids as a strategy to construct defined complex 3D structures. A similar approach has recently been applied to protein design, using orthogonal dimerizing coiled-coil segments as interacting modules. When concatenated into a single polypeptide chain, they self-assemble into the 3D structure defined by the topology of interacting modules within the chain. This approach allows the construction of geometric polypeptide scaffolds, bypassing the folding problem of compact proteins by relying on decoupled pairwise interactions. However, the folding pathway still needs to be optimized in order to allow rapid self-assembly under physiological conditions. Again the modularity of designed topological structures can be used to define the rules that guide the folding pathway of long polymers, such as DNA, based on the stability and topology of connected building modules. This approach opens the way towards incorporation of designed foldamers in biological systems and their functionalization.
COBISS.SI-ID: 5889050