Chiral Systems Made from DNA

Abstract

The very chemical structure of DNA that enables biological heredity and evolution has non-trivial implications for the self-organization of DNA molecules into larger assemblies and provides limitless opportunities for building functional nanostructures. This progress report discusses the natural organization of DNA into chiral structures and recent advances in creating synthetic chiral systems using DNA as a building material. How nucleic acid chirality naturally comes into play in a diverse array of situations is considered first, at length scales ranging from an individual nucleotide to entire chromosomes. Thereafter, chiral liquid crystal phases formed by dense DNA mixtures are discussed, including the ongoing efforts to understand their origins. The report then summarizes recent efforts directed toward building chiral structures, and other structures of complex topology, using the principle of DNA self-assembly. Discussed last are existing and proposed functional man-made nanostructures designed to either probe or harness DNA's chirality, from plasmonics and spintronics to biosensing.

Keywords: DNA origami; liquid crystals; nanotechnology; plasmonics; self‐assembly.

Figure 1

Chirality in biological nucleic acid systems. a) Stereochemical representations of d‐deoxyribose and d‐ribose. Red dots indicate the chirality centers. b) Dodecamers of double‐stranded A‐DNA, B‐DNA and Z‐DNA, based on PDB IDs 5MVT,^{[ 29 ]} 1RVI,^{[ 30 ]} and 1JES,^{[ 31 ]} respectively. c) An intercalated DNA structure, referred to as an “i‐motif,” based on PDB ID 2MRZ.^{[ 32 ]} d) Eukaryotic nucleosome based on PDB ID 1AOI.^{[ 33 ]} e) Archaeal superhelix based on PDB ID 5T5K.^{[ 34 ]} Reproduced with permission.^{[ 34 ]} Copyright 2017, The Authors, published by American Association for the Advancement of Science. f) Schematic of a plectoneme. g) DNA supercoiling generated during transcription by RNA polymerase (RNAP). Adapted with permission.^{[ 35 ]} Copyright 2012, Elsevier. h) Cryo‐EM structure of the herpes simplex virus 1 capsid (gray) and left‐handed‐spooled dsDNA genome (blue). Reproduced with permission.^{[ 36 ]} Copyright 2019, Springer Nature. i) A unicellular dinoflagellate and TEM photomicrograph of its chromosomes. Adapted with permission.^{[ 37 ]} Copyright 2010, American Society for Microbiology; Adapted with permission.^{[ 38 ]} Copyright 2013, Cell Press.

Figure 2

Chiral LC phases of dense DNA solutions. a) Schematic representation of the chiral nematic LC phase. The helical axes of the DNA molecules (cyan lines) are aligned to axes perpendicular to the chiral axis of the liquid crystal. As one translates along the chiral axis (gray arrow), the helical axis rotates (cyan axis). The rotation of the LC axis provides a distinct pattern in electron microscope images (right). Adapted with permission.^{[ 66 ]} Copyright 1996, Elsevier. b) All‐atom simulations reveal potential of mean force (PMF) between DNA double helices placed 26 Å apart as function of crossing angle α.^{[ 67 ]} The image depicts the simulation system containing a pair of 24‐bp DNA duplexes surrounded by 150 mM NaCl solution. Reproduced with permission under the terms of the Creative Commons Attribution 3.0 license.^{[ 67 ]} Copyright 2017, IOP Publishing. c) Filamentation of dsDNA through end‐to‐end stacking observed in all‐atom MD simulations.^{[ 68 ]} The left panel depicts an isolated pair of 10‐bp DNA helices after collapse into an end‐to‐end complex. The center panel shows a system containing 458 10‐bp DNA fragments with randomly generated initial positions. The right panel shows the long filaments that spontaneously formed during the 260‐ns simulation. Adapted with permission.^{[ 68 ]} Copyright 2012, Oxford University Press. d) The chirality of LC phases formed from short DNA fragments can be controlled by the sequence of the DNA. Each solid dot shows the critical concentration and helical wave vector for a DNA sequence (8–20 bp). The magenta and green dots indicate sequences giving left‐ and right‐handed LC chirality, respectively. The open magenta dot corresponds to long, 150 bp dsDNA. The open blue dots show the concentration dependence of the helical wave vector of a LC formed by the DNA of CGCGCCGGCGCG sequence. The black dot corresponds to an achiral DNA of AACGAATTCGTT sequence. Reproduced with permission.^{[ 65 ]} Copyright 2010, National Academy of Sciences. e) Six‐helix DNA bundles programmed using DNA origami to have variable internal twists (top) were condensed using dextran into LC phases with varying chiral properties (bottom).^{[ 69 ]} The pitch of the LC phase was seen to decrease with increasing concentration, as with LCs formed from short DNA duplexes (blue dots in (d)). Left‐ and right‐handed LCs were observed with the handedness of the LC correlating with the handedness of the bundle, but having a right‐handed bias, in contrast to LCs formed from bare DNA. Reproduced with permission.^{[ 69 ]} Copyright 2017, Springer Nature.

Figure 3

Topological DNA nanostructures. a) Schematic representation of a Holliday junction (left) and self‐assembly of many such junctions into a periodic lattice using the sticky‐ended cohesion principle (right). b) AFM images of double crossover (DX) DNA lattices; scale bars: 300 nm. Reproduced with permission.^{[ 86 ]} Copyright 1998, Springer Nature. c) A nanomechanical switch that changes its conformation as a dsDNA duplex linker (yellow) undergoes a B‐to‐Z (or vice versa) transition in response to modulation of the solution conditions. Reproduced with permission.^{[ 88 ]} Copyright 1999, Springer Nature. d) Schematics and TEM images of achiral and chiral DNA nanotubes obtained by wrapping DX tiles along different basis vectors. Reproduced with permission.^{[ 89 ]} Copyright 2004, American Chemical Society. e) Design and AFM images of diastereomeric DNA tetrahedron. Reproduced with permission.^{[ 90 ]} Copyright 2005, American Association for the Advancement of Science. f) Schematics and AFM images of left‐handed (top) and right‐handed Möbius strips made from DNA. Reproduced with permission.^{[ 91 ]} Copyright 2010, American Chemical Society. g) Design and AFM images of topologically catenated DNA circles. Reproduced with permission.^{[ 92 ]} Copyright 2011, Springer Nature. h) Schematics of dsDNA knots made from four‐way DNA junctions. Reproduced with permission.^{[ 93 ]} Copyright 2016, Springer Nature.

Figure 4

Self‐assembled DNA nanostructures of programmable twist. a) TEM images of twisted DNA origami bundles. The global twist was induced by changing the number of base pairs per turn of a DNA helix. Reproduced with permission.^{[ 111 ]} Copyright 2009, American Association for the Advancement of Science. b) Schematics of the induced chirality (top) and its characterization using fluorescence micrography (bottom) in a tile‐based DNA helix tube upon the addition or deletion of a base pair. Reproduced with permission.^{[ 112 ]} Copyright 2017, American Chemical Society. c) Schematics of the bottom‐up self‐assembly of a left‐handed DNA nanospring from 24‐helix DNA bundles labeled with membrane binding molecules (top) and TEM images of the assembled structure (bottom); scale bar: 50 nm. Reproduced with permission.^{[ 113 ]} Copyright 2018, John Wiley & Sons. d) Schematics and helium‐ion micrographs of a gigadalton, 450 nm diameter tube assembled from V‐bricks; scale bar: 50 nm. Reproduced with permission.^{[ 114 ]} Copyright 2017, Springer Nature. e) Schematics and AFM images of the right‐handed and left‐handed meta‐DNA nanostructure; scale bar: 100 nm. Adapted with permission.^{[ 115 ]} Copyright 2020, Springer Nature.

Figure 5

DNA‐based chiral plasmonic nanostructures. a) DNA pyramid decorated with four different‐sized gold nanoparticles. Reproduced with permission.^{[ 108 ]} Copyright 2009, American Chemical Society. b) DNA pyramid containing four different types of particles at its vertices. Reproduced with permission.^{[ 128 ]} Copyright 2012, American Chemical Society. c) Switching CD response of a gold–DNA nanostructure by dehydration. When solvated, DNA rods decorated with gold nanoparticles preferentially align normal to the surface (left). The direction of the CD response switches by 90° upon drying (right). The propagation direction of a circularly polarized light is indicated by arrows. Reproduced with permission.^{[ 129 ]} Copyright 2013, Springer Nature. d) Chiral plasmonic systems containing a pH‐sensitive DNA lock. The pH value controls the population of the right‐handed and left‐handed structures. Reproduced with permission.^{[ 130 ]} Copyright 2017, American Association for the Advancement of Science. e) Chiral plasmonic nanostructure can be switched between folded and extended states (top) and between right‐ and left‐handed states (bottom). The arrangement of gold nanoparticles attached to a DNA origami structure is reconfigured by the addition of DNA strands. Reproduced with permission.^{[ 131 ]} Copyright 2018, American Chemical Society. f) Plasmonic sensor of DNA concentration. Linking gold nanorods by analyte DNA tilts the nanorods with respect to each other (left), which is detected by measuring CD spectra (right). Reproducedand adapted under the terms of the Creative Commons CC‐BY license.^{[ 132 ]} Copyright 2013, Springer Nature.

Figure 6

Chiral‐induced spin selectivity. a) Mechanism of chiral spin selection with a helical molecule. Reproduced with permission.^{[ 147 ]} Copyright 2019, Springer Nature. b) Chiral spin selection using dsDNA. Top schematic: A permanent magnet is placed under a Ni substrate, forcing the spin of the substrate to align. An AFM tip placed in contact with a gold nanoparticle is used to measure the current between the nanoparticle‐DNA‐substrate.^{[ 148} , ^{149 ]} Bottom two panels: experimental measurements on a system shown in the schematic. Because DNA's chirality only allows one type of spin to transport from substrate to nanoparticle, and only the other type of spin from nanoparticle to substrate, the current passing from the substrate through dsDNA to the AFM tip is larger when the magnetic field is pointing down. Adapted with permission.^{[ 148} , ^{149 ]} Copyrights 2011 and 2012, American Chemical Society. c) Chiral molecule‐assisted water splitting. The presence of chiral molecules on the anode increases the efficiency of producing H₂. Reproduced with permission.^{[ 150 ]} Copyright 2015, American Chemical Society. d) Hypothetical memory device built using chiral molecules. Because of the spin selectivity of chiral molecules, the substrate is now magnetized by injecting one spin and pulling out the opposite spin. Chiral DNA nanostructures could potentially be used to build this type of a memory device. Reproduced with permission.^{[ 147 ]} Copyright 2019, Springer Nature.

Figure 7

Emerging application areas. a) Straight (upper) and twisted (lower) DNA origami nanotubes.^{[ 158 ]} b) The release rate of drug Dox from straight (S) and twisted (T) nano‐designs. a,b) Adapted with permission.^{[ 158 ]} Copyright 2012, American Chemical Society. c) Hypothetical mechanism of an actively‐switchable display. Each pixel contains a collection of chiral plasmonic origami nanostructures tethered to a transparent electrode surface illuminated by circularly polarized light. A small voltage is applied to make the electrode surface negative or positive, causing the helix to orient parallel or orthogonal to the incident light, respectively. When the helix is parallel to the light, the absorption is greater, making the pixel appear dark. DNA origami nanostructure designs adapted with permission.^{[ 129 ]} Copyright 2013, Springer Nature. d) Delivery of DNA to a nanopore using a chiral step‐defect graphene guide. Adapted with permission.^{[ 159 ]} Copyright 2019, Springer Nature.