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Building machines with DNA molecules

Abstract

In nature, DNA molecules carry the hereditary information. But DNA has physical and chemical properties that make it attractive for uses beyond heredity. In this Review, we discuss the potential of DNA for creating machines that are both encoded by and built from DNA molecules. We review the main methods of DNA nanostructure assembly, describe recent advances in building increasingly complex molecular structures and discuss strategies for creating machine-like nanostructures that can be actuated and move. We highlight opportunities for applications of custom DNA nanostructures as scientific tools to address challenges across biology, chemistry and engineering.

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Fig. 1: Design principles of DNA origami structures and higher-order self-assembly using origami tiles.
Fig. 2: Tile assembly of DNA nanostructures.
Fig. 3: SDR and SDR-based walkers.
Fig. 4: Reshaping nanostructures using SDR.
Fig. 5: Modes of molecular motion in DNA nanostructures.
Fig. 6: Applications of DNA nanostructures.
Fig. 7: Applications of DNA nanostructures.
Fig. 8: Natural biomolecular motors.

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Acknowledgements

The authors thank E. Feigl for making Figs. 1A and 1B. This work was financially supported by the Deutsche Forschungsgemeinschaft through the Gottfried-Wilhelm-Leibniz Program and by the European Commission through an ERC Consolidator Grant (#724261).

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Glossary

Self-assembly

A process through which the disordered components of a system organize themselves into a defined ordered state. The process is guided by minimization of the free energy of the system. Protein folding is an example of molecular self-assembly.

DNA nanotechnology

The design and self-assembly of DNA into pre-defined patterns and attempts to control the shapes and functions of the assembled nanostructures.

Rotaxanes

A class of mechanically interlocked molecules consisting of a ring entrapped between the two bulky ends of a dumbbell-shaped molecule.

Catenanes

A class of mechanically interlocked molecules comprising two or more interchained macrocyclic rings.

Brownian motors

A molecule or a molecular system that converts random Brownian motion to directional motion at the nanoscale by doing work on the environment.

DNA switches

Molecular switches made of DNA that transition between at least two distinct states using a trigger — for example, pH or metal ions.

Persistence lengths

A physical parameter indicating the stiffness of a polymer such as DNA, defined as the length over which the molecule behaves like a rigid rod.

Tiles

A DNA motif self-assembled from multiple single-stranded DNA oligomers to form a unit for further assembly of a nanostructure. There are usually one or more crossovers in each tile, rendering it more rigid.

Sticky-ended DNA

A DNA partial duplex with a single-stranded overhang that can hybridize to another, complementary single-stranded overhang, thus ‘sticking’ the two partial duplexes together.

DNA origamis

DNA nanostructures formed by folding a long single-stranded DNA scaffold via hybridization of many short DNA complements, known as staple strands.

Scaffold

The long single-stranded DNA template molecule, running through a whole DNA origami structure.

DNA crossovers

The points at which a DNA single strand exits its hybridization axis and enters an adjacent helix to continue its hybridization in the second helical axis.

Staple strands

The short DNA oligomers (usually 20–60 nucleotides long) used to staple different segments of the scaffold together and form a pre-determined geometry.

Segment lengths

Distances between two consecutive crossovers, which are a multiple of 7 bp in a honeycomb packing and a multiple of 8 bp in a square packing.

Wireframe tessellation

A DNA structure approximating a geometrical shape at its edges, through tiling of its surfaces by non-overlapping polygons that do not leave a gap.

Click contacts

Topological surface features of a DNA nanostructure, in the forms of protrusions and recessions that are capable of forming base-stacking interactions between two shape-complementary features, thus binding them.

DNAzyme

Also known as deoxyribozyme, DNA enzyme or catalytic DNA. A DNA oligonucleotide with a specific sequence that performs a chemical reaction similar to enzymes.

Strand displacement reaction

(SDR). A hybridization scheme in which a longer complement (fuel strand) displaces a shorter complement (output strand) via branch migration to form a more stable duplex.

Toehold

The unpaired segment of a partial DNA duplex, which can act as a seeding region to start a branch migration and a strand displacement reaction.

DNA walkers

Small DNA oligonucleotides that can move on a molecular track by a series of hybridization–dehybridization cycles.

Tensegrity

Originally an architectural concept; a particular type of structure that maintains its integrity through pervasive tensional forces. In a tensegrity, each individual structural element is under stress, but the overall structure is stable.

Aptamers

Oligonucleotides or small peptides that bind specifically to a target molecule.

Ratchet effects

The mechanisms by which molecular motors use random thermal noise to produce directional motion.

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Ramezani, H., Dietz, H. Building machines with DNA molecules. Nat Rev Genet 21, 5–26 (2020). https://doi.org/10.1038/s41576-019-0175-6

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