Crystalline Assemblies of DNA Nanostructures and Their Functional Properties

Abstract

Self-assembly presents a remarkable approach for creating intricate structures by positioning nanomaterials in precise locations, with control over molecular interactions. For example, material arrays with interplanar distances similar to the wavelength of light can generate structural color through complex interactions like scattering, diffraction, and interference. Moreover, enzymes, plasmonic nanoparticles, and luminescent materials organized in periodic lattices are envisioned to create functional materials with various applications. Focusing on structural DNA nanotechnology, here, we summarized the recent developments of two- and three-dimensional lattices made purely from DNA nanostructures. We review DNA-based monomer design for different lattices, guest molecule assembly, and inorganic material coating techniques and discuss their functional properties and potential applications in photonic crystals, nanoelectronics, and bioengineering as well as future challenges and perspectives.

Keywords: DNA nanotechnology; DNA origami; crystallization; photonic crystals; self-assembly.

Figure 1

Schematic representation of secondary structures of DNA and assembly strategies used in structural DNA nanotechnology. A Canonical B‐form double helical DNA double structure. B Holliday junction formed by the pairwise hybridization of four single DNA strands. C Triplex DNA displaying the triplex‐forming oligonucleotide (TFO) binding to the major groove of a dsDNA via Hoogsteen bonding. D Antiparallel G‐quadruplex formed in guanine‐rich DNA sequences. E DNA tile assembly with Holliday junctions. F DNA brick or single‐stranded tiles (SST) assembly. Single‐stranded DNA oligonucleotides with unique sequences are used as building blocks that can assemble into larger designed structures. G DNA origami.

Figure 2

Different types of 2D lattices formed with DNA tile nanostructures. A Self‐assembly of a DNA lattice using cross‐shaped 4×4 DNA tiles. B Three‐point‐star DNA motif and its two dimensional lattice assembly. C DNA six‐pointed‐star motif and the resulting 2D lattice after polymerization. D Finite‐sized array built with 5x5 square‐shaped DNA tiles. E 2D lattice assembled with coupled double crossovers motifs. F T‐shaped crossover (TC) tiles in which a double helical strut is introduced between two adjacent arms to sustain the angle between arms and release the possible curvature tension and facilitate the two‐dimensional lattice formation. Figure 2A is reproduced with permission from ref. [28]; Copyright 2003, The American Association for the Advancement of Science. Figure 2B, 2C, 2D are reproduced with from ref. [29], ref. [30], and ref. [32]; Copyright 2005, 2006, and 2005, American Chemical Society, respectively. Figure 2E is reproduced with permission from ref. [33]; Copyright 2022 Elsevier.

Figure 3

Two‐dimensional lattice assembly of DNA origami units and examples for reconfigurable 2D lattices. A Cross‐shaped DNA origami building blocks and their orthogonal assembly, resulting in a 2D array. B 2D arrays based on triangular DNA origami. C 2D honeycomb‐like lattices assembled from hexagonal DNA origami monomers. D Surface‐assisted DNA origami lattice formation on a mica‐supported lipid bilayer. E 2D lattice‐like structures formed from cholesterol‐functionalized DNA origami that were anchored on lipid membranes. F Lipid membrane‐assisted 2D lattice assembly of cross‐shaped DNA origami via blunt‐end stacking interactions. G pH‐responsive 2D lattices assembled from DNA origami building blocks containing triplex‐forming ‘pH‐latches’. H Dynamic DNA origami lattices formed by monomers with shape‐complementary protrusions and indentations. The switching between the different lattice states can be triggered by changes in the cation concentration or the temperature. Figure 3A and 3F are reproduced with permission from ref. [40] and ref. [52]; Copyright 2011 and 2018 WILEY‐VCH respectively. Figure 3B, 3C, and 3E are reproduced with permission from ref. [41], ref. [43], and ref. [50]; Copyright 2018, 2022, and 2015, American Chemical Society, respectively. Figure 3H is reproduced with permission from ref. [55] Copyright 2015, The American Association for the Advancement of Science.

Figure 4

Three‐dimensional lattice assembly of DNA tile motifs and examples for reconfigurable tile‐based 3D crystals. A 3D lattices assembled from DNA tensegrity triangles (lattice layout adapted with permission from PDB ID: 3GBI).[ ⁵⁶ , ⁷⁰ ] B Implementation of a crystal nanoactuator composed of DNA tensegrity triangle motifs that is responsive to different triggers such as temperature or ionic strength. C Geometry‐controlled self‐sorting into single‐motif crystals observed with triangular DNA motifs with different arm lengths. D 3D crystal structures based on DNA four‐arm motifs. E Layered crossover tiles forming 3D crystals. Tiles can be designed with different angles, resulting in different 2D and 3D lattice types. F Self‐assembly of amphiphilic DNA‐nanostars (C‐Stars) with cholesterol‐functionalized terminals into macroscopic single crystals via hydrophobic interactions. Figure 4C, 4D, 4E, 4F are reproduced with permission from ref. [36], ref. [66] ref. [68], and ref. [69]; Copyright 2022, 2016, 2018, 2017, American Chemical Society, respectively.

Figure 5

DNA origami lattices enabled by various monomeric origami nanoobjects. A Rhombohedral DNA origami lattices with large cavities assembled from tensegrity triangle building blocks. B 3D DNA origami “Wulff” crystals obtained from elongated octahedral monomers. C Different types of DNA origami lattices composed of polyhedral frames (tetrahedrons, cubes and bipyramids), together with the corresponding X‐ray scattering structure factors. D&E Model‐driven reverse design of DNA origami monomers for the desired lattice type using SAT‐assembly (a patchy‐particle interaction design algorithm based on constrained optimization solvers) and coarse‐grained simulations of DNA nanotechnology. Octahedral and icosahedral DNA origamis (E) are representative models for the experimental implementation of patchy particles to form lattices. Depicted are also SEM images for the resulting lattice structures from the experiment. Figure 5A is reproduced with permission from ref. [71]; Copyright 2018 WILEY‐VCH. Figure 5D and 5E are reproduced with permission from ref. [79] Copyright 2024, The American Association for the Advancement of Science.

Figure 6

Functionalization and functional properties of 2D DNA lattices. A 2D nanogrids assembled from cross‐shaped DNA tiles for the programmable self‐assembly of streptavidin protein arrays. B 2D Kagome lattice made from Holliday Junctions composed of four oligonucleotides. Upon addition of the DNA‐binding protein RuvA (image of the protein‐DNA‐complex adapted from PDB ID: 7X5A ^[87] ), the tiles switch to a square‐planar configuration, altering the lattice symmetry. C 2D DNA lattice assembled from Holliday Junctions as a template for the formation of ordered arrays of proteins to facilitate their structural analysis via cryo‐EM. D Monolayers of triangular DNA origami nanostructures deposited on mica surfaces, employed as nanolithography masks for proteins. E–H Different variants of 2D DNA lattice architectures with attached inorganic nanoparticles (NPs) using different shapes of DNA building blocks. The possibility to precisely control the inter‐particle spacings and the array geometry makes such assemblies interesting candidates particularly for optical/plasmonic metamaterials. E 2D arrays made from cross‐shaped tiles with conjugated Au NPs. F Formation of 2D ordered spatial arrangements of Au NPs using two variants of robust triangular DNA motifs. G Fabrication of ordered arrays of CdSe/ZnS QDs using 2D DNA lattices made from double‐crossover tiles. H Micron‐scale arrangement of Au NPs using 2D lattices from hexagonal DNA origami nanostructures. Figure 6A, 6C, 6D, 6F, and 6H are reproduced with permission from ref. [81], ref. [83], ref. [84], ref. [89] and ref. [91]; Copyright 2005, 2011, 2016, 2006, and 2016, American Chemical Society, respectively. Figure 6B, 6E, and 6G are reproduced with permission from ref. [82], ref. [88], and ref. [90]; Copyright 2005, 2006, and 2008 WILEY‐VCH.

Figure 7

Functionalization and functional properties of 3D DNA lattices. A DNA crystals assembled from triangular motifs acting as molecular sieves. The DNA crystals exhibit internal cavities of 9 nm, into which comparatively small proteins (here: GFP, 28 kDa) can diffuse while larger proteins (here: MBP‐RFP, 280 kDa) remain excluded from the crystals. B Spatial arrangement of GOx and HRP in octahedral building blocks and their assembly. C Incorporation of biologically active ferritin proteins into octahedral DNA origami monomers and subsequent polymerization into cubic crystals, creating functional 3D arrays of the ferritin proteins. D Covalent attachment of HPV, highlighted in yellow, to triangular DNA motifs and successful alignment of the HPV in the assembled DNA crystals, indicating potential applications for the construction of sophisticated nanodevices for optical and electrical purposes. E Co‐crystallization of regular and elongated octahedral DNA origami monomers, together with incorporated 10 nm Au NPs. F Testing the rigidity of 3D silica hybrid nanostructures obtained by growing a 4 to 20 nm thick silica shell on DNA origami lattice frameworks by performing in situ micro‐compression tests. G Assembly of cubic crystals from octahedral monomers that were silicified in solution prior to polymerization. Already a thin silica coating of only the monomers (and not the connections) increases the rigidity of the assembled crystals. H Coating of DNA origami crystals with silica and subsequently with superconducting niobium, paving the way towards the fabrication of 3D nano‐scale superconducting materials. I DNA origami diamond lattice formed from tetrapod‐shaped monomers. Additional silicification and coating with titanium dioxide by ALD resulted in photonic crystals with a tunable photonic band gap in the near UV range. J Silica‐coated DNA origami crystals as templates to form different types of metal and metal oxide frameworks via liquid‐ and vapor‐phase infiltration. Figure 7A and 7E are reproduced with permission from ref. [95] and ref. [100]; Copyright 2006 and 2020, American Chemical Society, respectively. Figure 7B is reproduced with permission from ref. [72]; Copyright 2020, Springer Nature. Figure 7D is reproduced with permission from ref. [99]; Copyright 2021 Wiley‐VCH. Figure 7I is reproduced with permission from ref. [104]; Copyright 2024, The American Association for the Advancement of Science.