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Dynamic and flexible nucleic acid models can provide current and future scientists with physical intuition for the structure of DNA and the ways that DNA and its synthetic mimics can be used to build self-assembling structures and advanced nanomachines. As more research labs and classrooms dive into the field of structural nucleic acid nanotechnology, students and researchers need access to interactive, dynamic, handheld models. Here, we present a 3D-printable kit for the construction of DNA and peptide nucleic acid (PNA). We have engineered a previous modular DNA kit to reduce costs while improving ease of assembly, flexibility, and robustness. We have also expanded the scope of available snap-together models by creating the first 3D-printable models of γPNA, an emerging material for nuclease- and protease-resistance nanotechnology. Building on previous research, representative nucleic acid duplexes were split into logical monomer segments, and atomic coordinates were used to create solid models for 3D printing. We used a human factors approach to customize 3 types of articulated snap-together connectors that allow for physically relevant motion characteristic of each interface in the model. Modules are easy to connect and separate manually but stay together when the model is manipulated. To greatly reduce cost, we bundled these segments for printing, and we created a miniaturized version that uses less than half the printing material to build. Our novel 3D-printed articulated snap-together models capture the flexibility and robustness of DNA and γPNA nanostructures. Resulting handheld helical models replicate the geometries in published structures and can now flex to form crossovers and allow biologically relevant zipping and unzipping to allow complex demonstrations of nanomachines undergoing strand displacement reactions. Finally, the same tools used to create these models can be readily applied to other types of backbones and nucleobases for endless research and education possibilities.

 

Peptide nucleic acids (PNAs) have primarily been used to achieve therapeutic gene modulation through antisense strategies since their design in the 1990s. However, the application of PNAs as a functional nanomaterial has been more recent. We recently reported thatγ‐modified peptide nucleic acids (γPNAs) could be used to enable formation of complex, self‐assembling nanofibers in select polar aprotic organic solvent mixtures. Here we demonstrate that distinctγPNA strands, each with a high density ofγ‐modifications can form complex nanostructures at constant temperatures within 30 minutes. Additionally, we demonstrate DNA‐assisted isothermal growth ofγPNA nanofibers, thereby overcoming a key hurdle for future scale‐up of applications related to nanofiber growth and micropatterning.

 

Nucleic acid-based materials enable sub-nanometer precision in self-assembly for fields including biophysics, diagnostics, therapeutics, photonics, and nanofabrication. However, structural DNA nanotechnology has been limited to substantially hydrated media. Transfer to organic solvents commonly used in polymer and peptide synthesis results in the alteration of DNA helical structure or reduced thermal stabilities. Here we demonstrate that gamma-modified peptide nucleic acids (γPNA) can be used to enable formation of complex, self-assembling nanostructures in select polar aprotic organic solvent mixtures. However, unlike the diameter-monodisperse populations of nanofibers formed using analogous DNA approaches,γPNA structures appear to form bundles of nanofibers. A tight distribution of the nanofiber diameters could, however, be achieved in the presence of the surfactant SDS during self-assembly. We further demonstrate nanostructure morphology can be tuned by means of solvent solution and by strand substitution with DNA and unmodified PNA. This work thereby introduces a science ofγPNA nanotechnology.

 

Magnetically-actuated swimming microrobots are an emerging tool for navigating and manipulating materials in confined spaces. Recent work has demonstrated that it is possible to build such systems at the micro and nanoscales using polymer microspheres, magnetic particles and DNA nanotechnology. However, while these materials enable an unprecedented ability to build at small scales, such systems often demonstrate significant polydispersity resulting from both the material variations and the assembly process itself. This variability makes it difficult to predict, let alone optimize, the direction or magnitude of microswimmer velocity from design parameters such as link shape or aspect ratio. To isolate questions of a swimmer's design from variations in its physical dimensions, we present a novel experimental platform using two-photon polymerization to build a two-link, buoyant milliswimmer with a fully customizable shape and integrated flexible linker (the swimmer is underactuated, enabling asymmetric cyclic motion and net translation). Our approach enables us to control both swimming direction and repeatability of swimmer performance. These studies provide ground truth data revealing that neither the first order nor second order models currently capture the key features of milliswimmer performance. We therefore use our experimental platform to develop design guidelines for tuning the swimming speeds, and we identify the following three approaches for increasing speed: (1) tuning the actuation frequency for a fixed aspect ratio, (2) adjusting the aspect ratio given a desired range of operating frequencies, and (3) using the weaker value of linker stiffness from among the values that we tested, while still maintaining a robust connection between the links. We also find experimentally that spherical two-link swimmers with dissimilar link diameters achieve net velocities comparable to swimmers with cylindrical links, but that two-link spherical swimmers of equal diameter do not. 

Abstract—This work demonstrates a novel approach to steering a magnetic swimming robot in two dimensions with a single pair of Maxwell coils. By leveraging the curvature of the magnetic field gradient, we achieve motion along two axes. This method allows us to control medical magnetic robots using only existing MRI technology, without requiring additional hard- ware or posing any additional risk to the patient. We implement a switching time optimization algorithm which generates a schedule of control inputs that direct the swimming robot to a goal location in the workspace. By alternating the direction of the magnetic field gradient produced by the single pair of coils per this schedule, we are able to move the swimmer to desired points in two dimensions. Finally, we demonstrate the feasibility of our approach with an experimental implementation on the millimeter scale and discuss future opportunities to expand this work to the microscale, as well as other control problems and real-world applications. 

Abstract—This work demonstrates a novel approach to steering a magnetic swimming robot in two dimensions with a single pair of Maxwell coils. By leveraging the curvature of the magnetic field gradient, we achieve motion along two axes. This method allows us to control medical magnetic robots using only existing MRI technology, without requiring additional hard- ware or posing any additional risk to the patient. We implement a switching time optimization algorithm which generates a schedule of control inputs that direct the swimming robot to a goal location in the workspace. By alternating the direction of the magnetic field gradient produced by the single pair of coils per this schedule, we are able to move the swimmer to desired points in two dimensions. Finally, we demonstrate the feasibility of our approach with an experimental implementation on the millimeter scale and discuss future opportunities to expand this work to the microscale, as well as other control problems and real-world applications. 

Cell penetrating peptides (CPPs), also known as protein transduction domains (PTDs), first identified ~25 years ago, are small, 6–30 amino acid long, synthetic, or naturally occurring peptides, able to carry variety of cargoes across the cellular membranes in an intact, functional form. Since their initial description and characterization, the field of cell penetrating peptides as vectors has exploded. The cargoes they can deliver range from other small peptides, full-length proteins, nucleic acids including RNA and DNA, liposomes, nanoparticles, and viral particles as well as radioisotopes and other fluorescent probes for imaging purposes. In this review, we will focus briefly on their history, classification system, and mechanism of transduction followed by a summary of the existing literature on use of CPPs as gene delivery vectors either in the form of modified viruses, plasmid DNA, small interfering RNA, oligonucleotides, full-length genes, DNA origami or peptide nucleic acids.