Publications associated with Self-assembled structures and devices
Programmable one-pot multistep organic synthesis using DNA junctions.
J Am Chem Soc 134 (2012) 1446-1449
A system for multistep DNA-templated synthesis is controlled by the sequential formation of DNA junctions. Reactants are attached to DNA adapters which are brought together by hybridization to DNA template strands. This process can be repeated to allow sequence-controlled oligomer synthesis while maintaining a constant reaction environment, independent of oligomer length, at each reaction step. Synthesis can take place in a single pot containing all required reactive monomers. Different oligomers can be synthesized in parallel in the same vessel, and the products of parallel synthesis can be ligated, reducing the number of reaction steps required to produce an oligomer of a given length.
A DNA-based molecular motor that can navigate a network of tracks.
Nat Nanotechnol 7 (2012) 169-173
Synthetic molecular motors can be fuelled by the hydrolysis or hybridization of DNA. Such motors can move autonomously and programmably, and long-range transport has been observed on linear tracks. It has also been shown that DNA systems can compute. Here, we report a synthetic DNA-based system that integrates long-range transport and information processing. We show that the path of a motor through a network of tracks containing four possible routes can be programmed using instructions that are added externally or carried by the motor itself. When external control is used we find that 87% of the motors follow the correct path, and when internal control is used 71% of the motors follow the correct path. Programmable motion will allow the development of computing networks, molecular systems that can sort and process cargoes according to instructions that they carry, and assembly lines that can be reconfigured dynamically in response to changing demands.
Sequence-specific synthesis of macromolecules using DNA-templated chemistry.
Chem Commun (Camb) 48 (2012) 5614-5616
Using a strand exchange mechanism we have prepared, by DNA templated chemistry, two 10-mers with defined and tunable monomer sequences. An optimized reaction protocol achieves 85% coupling yield per step, demonstrating that DNA-templated chemistry is a powerful tool for the synthesis of macromolecules with full sequence control.
A DNA network as an information processing system
International Journal of Molecular Sciences 13 (2012) 5125-5137
DNA cage delivery to mammalian cells.
ACS Nano 5 (2011) 5427-5432
DNA cages are nanometer-scale polyhedral structures formed by self-assembly from synthetic DNA oligonucleotides. Potential applications include in vivo imaging and the targeted delivery of macromolecules into living cells. We report an investigation of the ability of a model cage, a DNA tetrahedron, to enter live cultured mammalian cells. Cultured human embryonic kidney cells were treated with a range of fluorescently labeled DNA tetrahedra and subsequently examined using confocal microscopy and flow cytometry. Substantial uptake of tetrahedra into cells was observed both when the cells were treated with tetrahedra alone and when the cells were treated with a mixture of tetrahedra and a transfection reagent. Analysis of the subcellular localization of transfected tetrahedra using confocal microscopy and organelle staining indicates that the cages are located in the cytoplasm. FRET experiments indicate that the DNA cages remain substantially intact within the cells for at least 48 h after transfection. This is a first step toward the use of engineered DNA nanostructures to deliver and control the activity of cargoes within cells.
Reversible logic circuits made of DNA.
J Am Chem Soc 133 (2011) 20080-20083
We report reversible logic circuits made of DNA. The circuits are based on an AND gate that is designed to be thermodynamically and kinetically reversible and to respond nonlinearly to the concentrations of its input molecules. The circuits continuously recompute their outputs, allowing them to respond to changing inputs. They are robust to imperfections in their inputs.
DNA-templated protein arrays for single-molecule imaging.
Nano Lett 11 (2011) 657-660
Single-particle electron cryomicroscopy permits structural characterization of noncrystalline protein samples, but throughput is limited by problems associated with sample preparation and image processing. Three-dimensional density maps are reconstructed from high resolution but noisy images of individual molecules. We show that self-assembled DNA nanoaffinity templates can create dense, nonoverlapping arrays of protein molecules, greatly facilitating data collection. We demonstrate this technique using a G-protein-coupled membrane receptor, a soluble G-protein, and a signaling complex of both molecules.
Peptidomimetic bond formation by DNA-templated acyl transfer.
Org Biomol Chem 9 (2011) 1661-1666
The efficiencies of DNA-templated acyl transfer reactions between a thioester modified oligonucleotide and a series of amine and thiol based nucleophiles are directly compared. The reactivity of the nucleophile, reaction conditions (solvent, buffer, pH) and linker length all play important roles in determining the efficiency of the transfer reaction. Careful optimisation of the system enables the use of DNA-templated synthesis to form stable peptide-like bonds under mild aqueous conditions close to neutral pH.
Remote toehold: a mechanism for flexible control of DNA hybridization kinetics.
J Am Chem Soc 133 (2011) 2177-2182
Hybridization of DNA strands can be used to build molecular devices, and control of the kinetics of DNA hybridization is a crucial element in the design and construction of functional and autonomous devices. Toehold-mediated strand displacement has proved to be a powerful mechanism that allows programmable control of DNA hybridization. So far, attempts to control hybridization kinetics have mainly focused on the length and binding strength of toehold sequences. Here we show that insertion of a spacer between the toehold and displacement domains provides additional control: modulation of the nature and length of the spacer can be used to control strand-displacement rates over at least 3 orders of magnitude. We apply this mechanism to operate displacement reactions in potentially useful kinetic regimes: the kinetic proofreading and concentration-robust regimes.
DNA nanotechnology: geometrical self-assembly.
Nat Chem 3 (2011) 580-581
Direct observation of stepwise movement of a synthetic molecular transporter.
Nat Nanotechnol 6 (2011) 166-169
Controlled motion at the nanoscale can be achieved by using Watson-Crick base-pairing to direct the assembly and operation of a molecular transport system consisting of a track, a motor and fuel, all made from DNA. Here, we assemble a 100-nm-long DNA track on a two-dimensional scaffold, and show that a DNA motor loaded at one end of the track moves autonomously and at a constant average speed along the full length of the track, a journey comprising 16 consecutive steps for the motor. Real-time atomic force microscopy allows direct observation of individual steps of a single motor, revealing mechanistic details of its operation. This precisely controlled, long-range transport could lead to the development of systems that could be programmed and routed by instructions encoded in the nucleotide sequences of the track and motor. Such systems might be used to create molecular assembly lines modelled on the ribosome.
A programmable molecular robot.
Nano Lett 11 (2011) 982-987
We have developed a programmable and auton-omous molecular robot whose motion is fueled by DNA hybridization. Instructions determining the path to be followed are programmed into the fuel molecules, allowing precise control of cargo motion on a branched track.
Remote toehold: A mechanism for flexible control of DNA hybridization kinetics
Journal of the American Chemical Society 133 (2011) 2177-2182
Multistep DNA-templated reactions for the synthesis of functional sequence controlled oligomers.
Angew Chem Int Ed Engl 49 (2010) 7948-7951
Coordinated Chemomechanical Cycles: A Mechanism for Autonomous Molecular Motion (vol 101, 238101, 2008)
PHYS REV LETT 102 (2009) 139901
A facile method for reversibly linking a recombinant protein to DNA.
Chembiochem 10 (2009) 1551-1557
We present a facile method for linking recombinant proteins to DNA. It is based on the nickel-mediated interaction between a hexahistidine tag (His(6)-tag) and DNA functionalized with three nitrilotriacetic acid (NTA) groups. The resulting DNA-protein linkage is site-specific. It can be broken quickly and controllably by the addition of a chelating agent that binds nickel. We have used this new linker to bind proteins to a variety of DNA motifs commonly used in the fabrication of nanostructures by DNA self-assembly.
Kinetically controlled self-assembly of DNA oligomers.
J Am Chem Soc 131 (2009) 2422-2423
Metastable two-stranded DNA loops can be assembled into extended DNA oligomers by kinetically controlled self-assembly. Along the designed reaction pathway, the sequence of hybridization reactions is controlled by progressively revealing toeholds required to initiate strand-displacement reactions. The product length depends inversely on seed concentration and ranges from a few hundred to several thousand base-pairs.
Algorithmic Control: The Assembly and Operation of DNA Nanostructures and Molecular Machinery
ALGORITHMIC BIOPROCESSES (2009) 215-225
Mechanism for a directional, processive, and reversible DNA motor.
Small 5 (2009) 1513-1516