The ability to self-assemble nanodevices with programmed structural dynamics that can sense and respond to the local environment could enable transformative applications in fields including molecular robotics, nanomanufacturing, and nanomedicine. The responsive function of biomolecules is often driven by alterations in conformational distributions mediated by highly sensitive interactions with the local environment. Here, we mimic this approach by engineering inherent nanoscale structural dynamics (nanodynamics) into a DNA device that exhibits a distribution of conformations including two stable states separated by a transition state where the energy barrier height is on the scale of the thermal energy, kT = 4.1 pN·nm, enabling spontaneous transitions between states. We further establish design principles to regulate the equilibrium and kinetic behavior by substituting a few DNA strand components. We use single-molecule Förster resonance energy transfer measurements to show these nanodynamic properties are sensitive to sub-piconewton depletion forces in the presence of molecular crowding agents, and the device can measure depletion forces with a resolution of ∼100 fN. We anticipate that this approach of engineering nanodynamic DNA devices will enable molecular-scale systems that sense and respond to their local environment with extremely high sensitivity.
DNA origami is a rapidly emerging nanotechnology that enables researchers to create nanostructures with unprecedented geometric precision that have tremendous potential to advance a variety of fields including molecular sensing, robotics, and nanomedicine. Hence, many students could benefit from exposure to basic knowledge of DNA origami nanotechnology. However, due to the complexity of design, cost of materials, and cost of equipment, experiments with DNA origami have been limited mainly to research institutions in graduate level laboratories with significant prior expertise and well-equipped laboratories. This work focuses on overcoming critical barriers to translating DNA origami methods to educational laboratory settings. In particular, we present a streamlined protocol for fabrication and analysis of DNA origami nanostructures that can be carried out within a 2-hour laboratory course using low-cost equipment, much of which is readily available in educational laboratories and science classrooms. We focus this educational experiment module on a DNA origami nanorod structure that was previously developed for drug delivery applications. In addition to fabricating nanostructures, we demonstrate a protocol for students to analyze structures via gel electrophoresis using classroom-ready gel equipment. These results establish a basis to expose students to DNA origami nanotechnology and can enable or reinforce valuable learning milestones in fields such as biomaterials, biological engineering, and nanomedicine. Furthermore, introducing students to DNA nanotechnology and related fields can also have the potential to increase interest and future involvement by young students.
Deoxyribonucleic acid (DNA) origami is a method for the bottom-up self-assembly of complex nanostructures for applications, such as biosensing, drug delivery, nanopore technologies, and nanomechanical devices. Effective design of such nanostructures requires a good understanding of their mechanical behavior. While a number of studies have focused on the mechanical properties of DNA origami structures, considering defects arising from molecular self-assembly is largely unexplored. In this paper, we present an automated computational framework to analyze the impact of such defects on the structural integrity of a model DNA origami nanoplate. The proposed computational approach relies on a noniterative conforming to interface-structured adaptive mesh refinement (CISAMR) algorithm, which enables the automated transformation of a binary image of the nanoplate into a high fidelity finite element model. We implement this technique to quantify the impact of defects on the mechanical behavior of the nanoplate by performing multiple simulations taking into account varying numbers and spatial arrangements of missing DNA strands. The analyses are carried out for two types of loading: uniform tensile displacement applied on all the DNA strands and asymmetric tensile displacement applied to strands at diagonal corners of the nanoplate.
DNA origami (DO) nanotechnology has strong potential for applications including molecular sensing, drug delivery, and nanorobotics that rely on nanoscale structural precision and the ability to tune mechanical and dynamic properties. Given these emerging applications, there is a need to broaden access to and training on DO concepts, which would also provide an avenue to demonstrate engineering concepts such as kinematic motion and mechanical deformation as applied to nanotechnology and molecular systems. However, broader use in educational settings is hindered by the excessive cost and time of fabrication and analysis. Compliant, or deformable, DO is especially difficult to design and characterize in a cost-effective manner, because analysis often relies on advanced imaging methods to quantify structure conformations. Building on recent work establishing classroom-ready methods for DO fabrication and analysis, we developed an experiment module for classroom implementation focused on a DO compliant hinge joint. The module consists of folding three distinct joint conformations that can be evaluated via gel electrophoresis using portable and cost-effective equipment within ~120 min. To highlight the mechanical design, we present two beam-based models for describing the deformation that controls the joint angle. We envision that this module can broaden access to and interest in the mechanical design of DO.
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