Cell-targeted self-assembled DNA nanostructures

Gary B Braun

Cell-targeted self-assembled DNA nanostructures

2009, Journal of The American Chemical Society

Abstract

The ability to organize materials is a core goal of bionanotechnology. Biomedically relevant examples include the organization of cells into predictable architectures on surfaces 1,2 and the delivery of diverse molecules to cells. 3 Cell surface engineering 4 seeks to localize nanoscale materials such as proteins, 5 carbon nanotubes, 6 synthetic bioactive polymers, 7 vault nanoparticles, 8 and polyelectrolyte multilayer patches 9 onto cellular membranes. Cells have been assembled into microtissues using DNA-mediated interactions. 10 DNA scaffolds, which are nanoarrays built from repeating DNA motifs, have been used for multicomponent interactions 11 to position small peptides, 12 streptavidin, 13,14 antibodies, 15,16 and inorganic materials 17,18 on the array surface into controlled networks and to detect proteins, 19,20 DNA, 21 and RNA. We demonstrate how selfassembled DNA arrays can be directed to the surface of cells, first through biotin-streptavidin interactions and second through specific antibody-cell surface interactions. The versatile cargo-carrying ability of arrays for directing cell-surface interactions, cell-cell bridging, and positioning multiple cells onto a DNA fabric is explored.

these cellular compartments can be mimicked and constructed artificially, it will not only increase our fundamental knowledge of cellular metabolism, but could also be useful in broad applications ranging from chemical synthesis, functional biomaterials, and biofuel production to therapeutics and diagnosis. Rationally designed biomolecular self-assembly provides a promising route toward the development of synthetic cellular compartments. Over the past few decades, enzyme nanoreactors were developed which used multiple approaches including genetic fusion, [3] chemical crosslinking, [4] surface co-immobilization, [5] polymer vesicles, [6] and viruslike particles. [7] However, there remain several technical obstacles, including, limited control over the spatial arrangement, low encapsulation yield, inefficient transmembrane diffusion of substrates, lack of feedback control, and aggregation of vesicle shells. Deoxyribonucleic acid (DNA) is a self-assembling biopolymer that is directed by Watson-Crick base pairing to form predictable and double-helical secondary structures. Structural DNA nanotechnology began with Seeman's earlier work on branched DNA tiles. [8] Recent breakthroughs in scaffolded DNA origami [9] and single-stranded DNA tiles (SST) [10] have enabled the design and fabrication of sophisticated 1D, 2D, and 3D nanostructures. This has empowered the engineering of complex nanostructures with spatial confinements, such as curved containers, [11] nanoscale polyhedrons, [12] polyhedral meshes, [13] and periodic DNA crystals. [14] New methods were also developed to scale up DNA assemblies in size and quantity, [15] and to fold single-stranded nucleic acids into nanoscale shapes and devices. [16] Computational tools such as caDNAno [17] and CanDo [18] have been developed to facilitate the design of DNA nanostructures. One of the most attractive properties of DNA nanostructures is that they can be used as assembly templates to position other elements into diverse patterns at the nanoscale. As shown in Figure 1, DNA nanoscaffolds-directed assembly has the advantages of precisely defined geometry, sequence-addressable assembly, and adaption to various bioconjugations. Taking these advantages, DNA nanostructures were applied to assembling complex biomolecular complexes, such as the organization of multienzyme complexes, nanocaged enzymes, and biomimetic substrate channeling. [19] DNA nanostructures were also used to guide the assembly of membrane vesicles with controlled geometry and dynamics [20] and to engineer transmembrane nanopores. [21] The behaviors of living cells are governed by a series of regulated and confined biochemical reactions. The design and successful construction of synthetic cellular reactors can be useful in a broad range of applications that will bring significant scientific and economic impact. Over the past few decades, DNA self-assembly has enabled the design and fabrication of sophisticated 1D, 2D, and 3D nanostructures, and is applied to organizing a variety of biomolecular components into prescribed 2D and 3D patterns. In this Concept, the recent and exciting progress in DNA-scaffolded compartmentalizations and their applications in enzyme encapsulation, lipid membrane assembly, artificial transmembrane nanopores, and smart drug delivery are in focus. Taking advantage of these features promises to deliver breakthroughs toward the attainment of new synthetic and biomimetic reactors.

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Abstract

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