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Reconfigurable multi-component nanostructures built from DNA origami voxels

Luu, M. T.; Berengut, J.; Daljit Singh, J. K.; Coffi Dit Glieze, K.; Turner, M.; Skipper, K.; Meppat, S.; Abbas, A.; Fowler, H.; Close, W.; Doye, J. P. K.; Wickham, S. F. J.

2024-03-11 synthetic biology
10.1101/2024.03.10.584331 bioRxiv
Show abstract

In cells, proteins rapidly self-assemble into sophisticated nanomachines. Bio-inspired self-assembly approaches, such as DNA origami, have achieved complex 3D nanostructures and devices. However, current synthetic systems are limited by lack of structural diversity, low yields in hierarchical assembly, and challenges in reconfiguration. Here, we develop a modular system of DNA origami voxels with programmable 3D connections. We demonstrate multifunctional pools of up to 12 unique voxels that can assemble into many shapes, prototyping 50 structures. Multi-step assembly pathways with sequential reduction in conformational freedom were then explored to increase yield. Voxels were first assembled into flexible chains and then folded into rigid structures, increasing yield 100-fold. Furthermore, programmable switching of local connections between flexible and rigid states achieved rapid and reversible reconfiguration of global structures. We envision that foldable chains of DNA origami voxels can be integrated with scalable assembly methods to achieve new levels of complexity in reconfigurable nanomaterials.

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