Controlled transport of biomolecules across lipid bilayer membranes is of profound significance in biological processes. In cells, cargo exchange is mediated by dedicated channels that respond to triggers, undergo a nanomechanical change to reversibly open, and thus regulate cargo flux. Replicating these processes with simple yet programmable chemical means is of fundamental scientific interest. Artificial systems that go beyond nature’s remit in transport control and cargo are also of considerable interest for biotechnological applications but challenging to build. Here, we describe a synthetic channel that allows precisely timed, stimulus-controlled transport of folded and functional proteins across bilayer membranes. The channel is made via DNA nanotechnology design principles and features a 416 nm2 opening cross-section and a nanomechanical lid which can be controllably closed and re-opened via a lock-and-key mechanism. We envision that the functional DNA device may be used in highly sensitive biosensing, drug delivery of proteins, and the creation of artificial cell networks.

Programming self-assembled designer DNA crystals with various lattices and functions is one of the most important goals for nanofabrication using nucleic acids. The resulting porous materials possess atomic precision for several potential applications that rely on crystalline lattices and cavities. Herein, we present a rationally designed and self-assembled 3D DNA crystal lattice with hexagonal symmetry. In our design, two 21-base oligonucleotides are used to form a duplex motif that further assembles into a 3D array. The interactions between the strands are programmed using Watson-Crick base-pairing. The six-fold symmetry, as well as the chirality, is directed by the Holliday junctions formed between the duplex motifs. The rationally designed DNA crystal provides a new avenue that could create self-assembled macromolecular 3D crystalline lattices with atomic precision. In addition, the structure contains a highly organized array of well-defined cavities that are suitable for future applications with immobilized guests.

DNA nanotechnology has been proven to be a powerful platform to assist the development of imaging probes for biomedical research. The attractive features of DNA nanostructures, such as nanometer precision, controllable size, programmable functions, and biocompatibility, have enabled researchers to design and customize DNA nanoprobes for bioimaging applications. However, DNA probes with low molecular weights (e.g., 10–100 nt) generally suffer from low stability in physiological buffer environments. To improve the stability of DNA nanoprobes in such environments, DNA nanostructures can be designed with relatively larger sizes and defined shapes. In addition, the established modification methods for DNA nanostructures are also essential in enhancing their properties and performances in a physiological environment. In this review, we begin with a brief recap of the development of DNA nanostructures including DNA tiles, DNA origami, and multifunctional DNA nanostructures with modifications. Then we highlight the recent advances of DNA nanostructures for bioimaging, emphasizing the latest developments in probe modifications and DNA-PAINT imaging. Multiple imaging modules for intracellular biomolecular imaging and cell membrane biomarkers recognition are also summarized. In the end, we discuss the advantages and challenges of applying DNA nanostructures in bioimaging research and speculate on its future developments.

Improving the precision and function of encapsulating three-dimensional (3D) DNA nanostructures via curved geometries could have transformative impacts on areas such as molecular transport, drug delivery, and nanofabrication. However, the addition of non-rasterized curvature escalates design complexity without algorithmic regularity, and these challenges have limited the ad hoc development and usage of previously unknown shapes. In this work, we develop and automate the application of a set of previously unknown design principles that now includes a multilayer design for closed and curved DNA nanostructures to resolve past obstacles in shape selection, yield, mechanical rigidity, and accessibility. We design, analyze, and experimentally demonstrate a set of diverse 3D curved nanoarchitectures, showing planar asymmetry and examining partial multilayer designs. Our automated design tool implements a combined algorithmic and numerical approximation strategy for scaffold routing and crossover placement, which may enable wider applications of general DNA nanostructure design for nonregular or oblique shapes.

We present here the combination of experimental and computational modeling tools for the design and characterization of protein−DNA hybrid nanostructures. Our work incorporates several features in the design of these nanostructures: (1) modeling of the protein−DNA linker identity and length; (2) optimizing the design of protein−DNA cages to account for mechanical stresses; (3) probing the incorporation efficiency of protein−DNA conjugates into DNA nanostructures. The modeling tools were experimentally validated using structural characterization methods like cryo-TEM and AFM. Our method can be used for fitting low-resolution electron density maps when structural insights cannot be deciphered from experiments, as well as enable insilico validation of nanostructured systems before their experimental realization. These tools will facilitate the design of complex hybrid protein−DNA nanostructures that seamlessly integrate the two different biomolecules.