Switching the topology of DNA building blocks (the number, connectivity, and spatial arrangement of individual strands that comprise a given structure) is essential to controlling the nanoscale architectures that they can form. The linear and cyclic topologies of DNA are two of its most ubiquitous architectures and are traditionally synthesized via ligation in a competition between inter- and intramolecular interactions. However, the conditions required to deliberately and dynamically switch between cyclization and linear polymerization are unknown. Yet, by facilitating such an interconversion, oligonucleotide constructs could be used as versatile switching modalities for driving higher ordered architectural outcomes. In this work, we explore oligonucleotides alone, and then protein-modified oligonucleotides, to investigate the conditions necessary to drive topological changes from a dynamic library of DNA architectures in equilibrium (e.g., dimers, trimers, hexamers, and larger oligomers). Non-hybridizing, single-stranded “spacer” regions are incorporated into pairs of single-stranded DNA monomers and favor the synthesis of cyclic dimers due to increased flexibility, with even a single nucleotide spacer increasing the preference for the cyclic structure nine-fold. In contrast, the addition of duplexer strands to rigidify the spacers results in spontaneous linear polymerization. Visualized by atomic force microscopy, the addition or displacement of duplexer strands enables dynamic rigidity control, leading to deliberate, reversible switching between two topological states<i> in situ</i>. Finally, this control is leveraged by conjugating proteins onto the designed oligonucleotides and dynamically modulating the architecture of protein assemblies between bivalent and polyvalent states, enabling new avenues for designing stimuli-responsive hybrid materials.

Reconfigurable topologies in multivalent DNA-protein assemblies

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ACS Fall 2022

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