The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

We introduce the concept of hybridization chain reaction (HCR), in which stable DNA monomers assemble only upon exposure to a target DNA fragment. In the simplest version of this process, two stable species of DNA hairpins coexist in solution until the introduction of initiator strands triggers a cascade of hybridization events that yields nicked double helices analogous to alternating copolymers. The average molecular weight of the HCR products varies inversely with initiator concentration. Amplification of more diverse recognition events can be achieved by coupling HCR to aptamer triggers. This functionality allows DNA to act as an amplifying transducer for biosensing applications.

/pdf/triggered-amplification-by-hybridization-chain-reaction-573lm4jqdm.pdf

Triggered amplification by hybridization chain reaction.

A DNA nanostructure consisting of four four-arm junctions oriented with a square aspect ratio was designed and constructed. Programmable self-assembly of 4 × 4 tiles resulted in two distinct lattice morphologies: uniform-width nanoribbons and two-dimensional nanogrids, which both display periodic square cavities. Periodic protein arrays were achieved by templated self-assembly of streptavidin onto the DNA nanogrids containing biotinylated oligonucleotides. On the basis of a two-step metallization procedure, the 4 × 4 nanoribbons acted as an excellent scaffold for the production of highly conductive, uniform-width, silver nanowires.

https://www.phy.duke.edu/%7Egleb/Pdf_FILES/DNA_science.pdf

DNA-Templated Self-Assembly of Protein Arrays and Highly Conductive Nanowires

The programmable and reliable hybridization of DNA strands has enabled the preparation of a wide variety of structures. This Review discusses how, in addition to these static assemblies, the process of displacing — and ultimately replacing — strands also makes possible the construction of dynamic systems such as logic gates or autonomous walkers.

/pdf/dynamic-dna-nanotechnology-using-strand-displacement-3n3nflfseh.pdf

Dynamic DNA nanotechnology using strand-displacement reactions

Consolidation is the progressive postacquisition stabilization of long-term memory. The term is commonly used to refer to two types of processes: synaptic consolidation, which is accomplished within the first minutes to hours after learning and occurs in all memory systems studied so far; and system consolidation, which takes much longer, and in which memories that are initially dependent upon the hippocampus undergo reorganization and may become hippocampal-independent. The textbook account of consolidation is that for any item in memory, consolidation starts and ends just once. Recently, a heated debate has been revitalized on whether this is indeed the case, or, alternatively, whether memories become labile and must undergo some form of renewed consolidation every time they are activated. This debate focuses attention on fundamental issues concerning the nature of the memory trace, its maturation, persistence, retrievability, and modifiability.

The Neurobiology of Consolidations, Or, How Stable is the Engram?

We present an experimental realization of a molecular walking motor built from DNA. The device consists of a biped and a well-defined track where it walks. Input DNA strands act as a convenient interface to allow precise control of the biped walking forward or backward. Psoralen molecules are attached to the ends of the feet in synthesis. When irradiated, the psoralen molecules cross-link strands covalently, allowing unambiguous determination of the state of the walker.

A precisely controlled DNA biped walking device

Nanoscale components can be self-assembled into static three-dimensional structures, arrays and clusters using biomolecular motifs. The structural plasticity of biomolecules and the reversibility of their interactions can also be used to make nanostructures that are dynamic, reconfigurable and responsive. DNA has emerged as an ideal biomolecular motif for making such nanostructures, partly because its versatile morphology permits in situ conformational changes using molecular stimuli. This has allowed DNA nanostructures to exhibit reconfigurable topologies and mechanical movement. Recently, researchers have begun to translate this approach to nanoparticle interfaces, where, for example, the distances between nanoparticles can be modulated, resulting in a distance-dependent plasmonic response. Here, we report the assembly of nanoparticles into three-dimensional superlattices and dimer clusters, using a reconfigurable DNA device that acts as an interparticle linkage. The interparticle distances in the superlattices and clusters can be modified, while preserving structural integrity, by adding molecular stimuli (simple DNA strands) after the self-assembly processes has been completed. Both systems were found to switch between two distinct rigid states, but a transition to a flexible device configuration within a superlattice showed a significant hysteresis.

Switching binary states of nanoparticle superlattices and dimer clusters by DNA strands

When rats received a brief footshock upon stepping off an elevated platform, and an electroconvulsive shock 30 seconds or 6 hours afterward, amnesia was not observed 24 hours later. If a second footshock (noncontingent) was delivered 0.5 second before the electroconvulsive shock, amnesia was observed. The amnesia was temporary if conditioning was strong and permanent if conditioning was weak.

Amnesia: a function of the temporal relation of footshock to electroconvulsive shock.

Amyloid fibrils are ordered, insoluble protein aggregates that are associated with neurodegenerative conditions such as Alzheimer's disease. The fibrils have a common rod-like core structure, formed from an elongated stack of β-strands, and have a rigidity similar to that of silk (Young's modulus of 0.2-14 GPa). They also exhibit high thermal and chemical stability and can be assembled in vitro from short synthetic non-disease-related peptides. As a result, they are of significant interest in the development of self-assembled materials for bionanotechnology applications. Synthetic DNA molecules have previously been used to form intricate structures and organize other materials such as metal nanoparticles and could in principle be used to nucleate and organize amyloid fibrils. Here, we show that DNA origami nanotubes can sheathe amyloid fibrils formed within them. The fibrils are built by modifying the synthetic peptide fragment corresponding to residues 105-115 of the amyloidogenic protein transthyretin and a DNA origami construct is used to form 20-helix DNA nanotubes with sufficient space for the fibrils inside. Once formed, the fibril-filled nanotubes can be organized onto predefined two-dimensional platforms via DNA-DNA hybridization interactions.

Amyloid fibrils nucleated and organized by DNA origami constructions

We present geometry based design strategies for DNA nanostructures. The strategies have been implemented with GIDEON—a graphical integrated development environment for oligonucleotides. GIDEON has a highly flexible graphical user interface that facilitates the development of simple yet precise models, and the evaluation of strains therein. Models are built on a simple model of undistorted B-DNA double-helical domains. Simple point and click manipulations of the model allow the minimization of strain in the phosphate-backbone linkages between these domains and the identification of any steric clashes that might occur as a result. Detailed analysis of 3D triangles yields clear predictions of the strains associated with triangles of different sizes. We have carried out experiments that confirm that 3D triangles form well only when their geometrical strain is less than 4% deviation from the estimated relaxed structure. Thus geometry-based techniques alone, without detailed energetic considerations, can be used to explain certain general trends in DNA structure formation. We have used GIDEON to build detailed models of double crossover and triple crossover molecules, evaluating the non-planarity associated with base tilt and junction misalignments. Computer modeling using a graphical user interface overcomes the limited precision of physical models for larger systems, and the limited interaction rate associated with earlier, command-line driven software.

/pdf/architecture-with-gideon-a-program-for-design-in-structural-37xne6b4io.pdf

William B. Sherman

Papers

A precisely controlled DNA biped walking device

Switching binary states of nanoparticle superlattices and dimer clusters by DNA strands

Amnesia: a function of the temporal relation of footshock to electroconvulsive shock.

Amyloid fibrils nucleated and organized by DNA origami constructions

Architecture with GIDEON, a program for design in structural DNA nanotechnology.