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DNA origami

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From Molecupedia, the encyclopedia of very small things
Method of folding a long strand of DNA into a designed shape with many short staple strands

DNA origami is a method of making objects from DNA by folding one long single strand, the scaffold, with a large number of short synthetic strands, the staples. Each staple binds two or more distant stretches of the scaffold and pulls them together, and the sum of hundreds of such pulls fixes the shape. Paul Rothemund introduced the method in 2006 with a scaffold of 7 kilobases and over 200 staples. The resulting structures were about 100 nm across and matched shapes such as squares, disks and five-pointed stars with a resolution of 6 nm.[1] Once the strands are synthesized and mixed, they assemble in a single step.

The method is used wherever a nanometer-scale object with addressable surfaces is useful. In nanopore research, DNA origami has been used as a label, as a plug, as a channel and as a motor.

Three steps: a long coiled scaffold strand, the strand with many short staples attached at distant points, and a flat folded rectangle made of parallel double helices
The principle of DNA origami: one long scaffold strand is held in a chosen path by many short staple strands. Schematic and not to scale.

Method

The scaffold is usually the single-stranded genome of the bacteriophage M13mp18, which has 7,249 nucleotides. Paired with staples, it makes a double helix 2.5 µm long, which the finished structure packs into a plate about 100 nm across. A program lays the scaffold out as a path through the shape, in rows of parallel double helices, and then computes the staples, each complementary to a few stretches of the path. Rothemund described the design as raster-filling the shape with the scaffold. Each staple can serve as a pixel 6 nm across, so a structure can be programmed to bear words and images on its surface, and structures can be programmed to join into larger assemblies, including periodic lattices.[1] Design software for three-dimensional structures, caDNAno, was published in 2009.[2]

Folding needs patience and salt. The first three-dimensional structures, built from pleated layers of helices on a honeycomb lattice, required "week-long folding times and calibrated monovalent and divalent cation concentrations".[3]

Background and development

Nadrian Seeman proposed in 1982 that branched junctions of DNA could be assembled into lattices, the founding idea of DNA nanotechnology.[4] In 2004 Shih, Quispe and Joyce folded a single strand of 1.7 kilobases into an octahedron with the help of a few short strands.[5] Rothemund's origami followed two years later.

Three-dimensional origami arrived in 2009 with the honeycomb structures and with twisted and curved shapes.[6] In 2012 Peng Yin's group dropped the scaffold. Each 32-nucleotide "brick" of one set binds four neighbors, and each pairing of 8 base pairs defines a voxel of 2.5 by 2.5 by 2.7 nm in a canvas 10 voxels on a side, from which 102 shapes were built.[7] A second paper from the group built complex two-dimensional shapes from single-stranded tiles.[8]

Nanopore uses

Origami can serve as a label. In 2016 N. A. W. Bell and Ulrich Keyser designed carrier molecules in which groups of hairpin loops along the DNA mark bits that a pore reads as spikes in the current, and used them to detect antibodies; see DNA barcode (nanopore).[9] Origami structures also change what a pore does. A plate with an aperture placed over a solid-state pore turned it into a device for sensing macromolecules, and the aperture could be chemically addressed to detect DNA of a given sequence.[10] Combined with glass nanocapillaries, origami formed pores of adjustable size that controlled the folding of double-stranded DNA as it passed.[11]

Origami can be the pore. In 2012 a stem of scaffolded DNA that spanned a lipid membrane, with a barrel-shaped cap held to the membrane by 26 cholesterol groups, gave channels with conductances on the order of 1 nS and gating like that of natural ion channels.[12] In 2024 a nanoturbine of DNA origami with three chiral blades, 24 to 27 nm in height and diameter, used the voltage across a nanopore to turn DNA bundles at up to 10 revolutions per second, in a direction set by the chirality of the blades.[13]

At Molecular Reality

Molecular Reality Corporation meets DNA origami as a sample and as a data set. The 2022 memo on the planned game Genomic Ranger lists "DNA origami" among its samples.[14] The company's machine-learning experiments use recordings of barcoded carriers from the Cambridge group; see QuipuNet. And its atlas of the field, The Hole World, draws 25 of its 2,112 entries as origami plates with a hole in them.[15]

See also

References

  1. ^ a b Rothemund, P. W. K. (2006). "Folding DNA to create nanoscale shapes and patterns". Nature 440 (7082): 297-302. doi:10.1038/nature04586.
  2. ^ Douglas, S. M.; et al. (2009). "Rapid prototyping of 3D DNA-origami shapes with caDNAno". Nucleic Acids Research 37 (15): 5001-5006. doi:10.1093/nar/gkp436.
  3. ^ Douglas, S. M.; et al. (2009). "Self-assembly of DNA into nanoscale three-dimensional shapes". Nature 459 (7245): 414-418. doi:10.1038/nature08016.
  4. ^ Seeman, N. C. (1982). "Nucleic acid junctions and lattices". Journal of Theoretical Biology 99 (2): 237-247. doi:10.1016/0022-5193(82)90002-9.
  5. ^ Shih, W. M.; Quispe, J. D.; Joyce, G. F. (2004). "A 1.7-kilobase single-stranded DNA that folds into a nanoscale octahedron". Nature 427 (6975): 618-621. doi:10.1038/nature02307.
  6. ^ Dietz, H.; Douglas, S. M.; Shih, W. M. (2009). "Folding DNA into twisted and curved nanoscale shapes". Science 325 (5941): 725-730. doi:10.1126/science.1174251.
  7. ^ Ke, Y.; Ong, L. L.; Shih, W. M.; Yin, P. (2012). "Three-dimensional structures self-assembled from DNA bricks". Science 338 (6111): 1177-1183. doi:10.1126/science.1227268.
  8. ^ Wei, B.; Dai, M.; Yin, P. (2012). "Complex shapes self-assembled from single-stranded DNA tiles". Nature 485 (7400): 623-626. doi:10.1038/nature11075.
  9. ^ Bell, N. A. W.; Keyser, U. F. (2016). "Digitally encoded DNA nanostructures for multiplexed, single-molecule protein sensing with nanopores". Nature Nanotechnology 11 (7): 645-651. doi:10.1038/nnano.2016.50.
  10. ^ Wei, R.; Martin, T. G.; Rant, U.; Dietz, H. (2012). "DNA origami gatekeepers for solid-state nanopores". Angewandte Chemie International Edition 51 (20): 4864-4867. doi:10.1002/anie.201200688.
  11. ^ Hernández-Ainsa, S.; et al. (2013). "DNA origami nanopores for controlling DNA translocation". ACS Nano 7 (7): 6024-6030. doi:10.1021/nn401759r.
  12. ^ Langecker, M.; et al. (2012). "Synthetic lipid membrane channels formed by designed DNA nanostructures". Science 338 (6109): 932-936. doi:10.1126/science.1225624.
  13. ^ Shi, X.; et al. (2024). "A DNA turbine powered by a transmembrane potential across a nanopore". Nature Nanotechnology 19 (3): 338-344. doi:10.1038/s41565-023-01527-8.
  14. ^ "Early Releases on Maxine's Quest". Molecular Reality Corporation. 2022.
  15. ^ "The Hole World: Molecular Sensing Atlas". Molecular Reality Corporation. September 26, 2026.
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