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The very chemical structure of DNA that enables biological heredity and evolution has non‐trivial implications for the self‐organization of DNA molecules into larger assemblies and provides limitless opportunities for building functional nanostructures. This progress report discusses the natural organization of DNA into chiral structures and recent advances in creating synthetic chiral systems using DNA as a building material. How nucleic acid chirality naturally comes into play in a diverse array of situations is considered first, at length scales ranging from an individual nucleotide to entire chromosomes. Thereafter, chiral liquid crystal phases formed by dense DNA mixtures are discussed, including the ongoing efforts to understand their origins. The report then summarizes recent efforts directed toward building chiral structures, and other structures of complex topology, using the principle of DNA self‐assembly. Discussed last are existing and proposed functional man‐made nanostructures designed to either probe or harness DNA's chirality, from plasmonics and spintronics to biosensing.

 

2D nanoslit devices, where two crystals with atomically flat surfaces are separated by only a few nanometers, have attracted considerable attention because their tunable control over the confinement allows for the discovery of unusual transport behavior of gas, water, and ions. Here, the passage of double‐stranded DNA molecules is studied through nanoslits fabricated from exfoliated 2D materials, such as graphene or hexagonal boron nitride, and the DNA polymer behavior is examined in this tight confinement. Two types of events are observed in the ionic current: long current blockades that signal DNA translocation and short spikes where DNA enters the slits but withdraws. DNA translocation events exhibit three distinct phases in their current‐blockade traces—loading, translation, and exit. Coarse‐grained molecular dynamics simulation allows the different polymer configurations of these phases to be identified. DNA molecules, including folds and knots in their polymer structure, are observed to slide through the slits with near‐uniform velocity without noticeable frictional interactions of DNA with the confining graphene surfaces. It is anticipated that this new class of 2D‐nanoslit devices will provide unique ways to study polymer physics and enable lab‐on‐a‐chip biotechnology.

 

Flowing fluid past chiral objects has been used for centuries to power rotary motion in man-made machines. By contrast, rotary motion in nanoscale biological or chemical systems is produced by biasing Brownian motion through cyclic chemical reactions. Here we show that a chiral biological molecule, a DNA or RNA duplex rotates unidirectionally at billions of revolutions per minute when an electric field is applied along the duplex, with the rotation direction being determined by the chirality of the duplex. The rotation is found to be powered by the drag force of the electro-osmotic flow, realizing the operating principle of a macroscopic turbine at the nanoscale. The resulting torques are sufficient to power rotation of nanoscale beads and rods, offering an engineering principle for constructing nanoscale systems powered by electric field. 

The development of the DNA origami technique has directly inspired the idea of using three-dimensional DNA cages for the encapsulation and targeted delivery of drug or cargo molecules. The cages would be filled with molecules that would be released at a site of interest upon cage opening triggered by an external stimulus. Though different cage variants have been developed, efficient loading of DNA cages with freely-diffusing cargo molecules that are not attached to the DNA nanostructure and their efficient retention within the cages has not been presented. Here we address these challenges using DNA origami nanotubes formed by a double-layer of DNA helices that can be sealed with tight DNA lids at their ends. In a first step we attach DNA-conjugated cargo proteins to complementary target strands inside the DNA tubes. After tube sealing, the cargo molecules are released inside the cavity using toehold-mediated strand displacement by externally added invader strands. We show that DNA invaders are rapidly entering the cages through their DNA walls. Retention of ∼70 kDa protein cargo molecules inside the cages was, however, poor. Guided by coarse-grained simulations of the DNA cage dynamics, a tighter sealing of the DNA tubes was developed which greatly reduced the undesired escape of cargo proteins. These improved DNA nanocages allow for efficient encapsulation of medium-sized cargo molecules while remaining accessible to small molecules that can be used to trigger reactions, including a controlled release of the cargo via nanocage opening. 

Nanoscale channels built with DNA enable leakless transport of substances across several micrometers. 

RNA fibers are a class of biomaterials that can be assembled using HIV-like kissing loop interactions. Because of the programmability of molecular design and low immunorecognition, these structures present an interesting opportunity to solve problems in nanobiotechnology and synthetic biology. However, the experimental tools to fully characterize and discriminate among different fiber structures in solution are limited. Herein, we utilize solid-state nanopore experiments and Brownian dynamics simulations to characterize and distinguish several RNA fiber structures that differ in their degrees of branching. We found that, regardless of the electrolyte type and concentration, fiber structures that have more branches produce longer and deeper ionic current blockades in comparison to the unbranched fibers. Experiments carried out at temperatures ranging from 20–60 °C revealed almost identical distributions of current blockade amplitudes, suggesting that the kissing loop interactions in fibers are resistant to heating within this range. 

Modeling and simulation has become an invaluable partner in development of nanopore sensing systems. The key advantage of the nanopore sensing method – the ability to rapidly detect individual biomolecules as a transient reduction of the ionic current flowing through the nanopore – is also its key deficiency, as the current signal itself rarely provides direct information about the chemical structure of the biomolecule. Complementing experimental calibration of the nanopore sensor readout, coarse-grained and all-atom molecular dynamics simulations have been used extensively to characterize the nanopore translocation process and to connect the microscopic events taking place inside the nanopore to the experimentally measured ionic current blockades. Traditional coarse-grained simulations, however, lack the precision needed to predict ionic current blockades with atomic resolution whereas traditional all-atom simulations are limited by the length and time scales amenable to the method. Here, we describe a multi-resolution framework for modeling electric field-driven passage of DNA molecules and nanostructures through to-scale models of synthetic nanopore systems. We illustrate the method by simulating translocation of double-stranded DNA through a solid-state nanopore and a micron-scale slit, capture and translocation of single-stranded DNA in a double nanopore system, and modeling ionic current readout from a DNA origami nanostructure passage through a nanocapillary. We expect our multi-resolution simulation framework to aid development of the nanopore field by providing accurate, to-scale modeling capability to research laboratories that do not have access to leadership supercomputer facilities. 

Abstract Biological molecular motors transform chemical energy into mechanical work by coupling cyclic catalytic reactions to large-scale structural transitions. Mechanical deformation can be surprisingly efficient in realizing such coupling, as demonstrated by the F 1 F O ATP synthase. Here, we describe a synthetic molecular mechanism that transforms a rotary motion of an asymmetric camshaft into reciprocating large-scale transitions in a surrounding stator orchestrated by mechanical deformation. We design the mechanism using DNA origami, characterize its structure via cryo-electron microscopy, and examine its dynamic behavior using single-particle fluorescence microscopy and molecular dynamics simulations. While the camshaft can rotate inside the stator by diffusion, the stator’s mechanics makes the camshaft pause at preferred orientations. By changing the stator’s mechanical stiffness, we accelerate or suppress the Brownian rotation, demonstrating an allosteric coupling between the camshaft and the stator. Our mechanism provides a framework for manufacturing artificial nanomachines that function because of coordinated movements of their components.