Yuanchen Dong

DNA nanotechnology based on i-motif structures.

CONSPECTUS: Most biological processes happen at the nanometer scale, and understanding the energy transformations and material transportation mechanisms within living organisms has proved challenging. To better understand the secrets of life, researchers have investigated artificial molecular motors and devices over the past decade because such systems can mimic certain biological processes. DNA nanotechnology based on i-motif structures is one system that has played an important role in these investigations. In this Account, we summarize recent advances in functional DNA nanotechnology based on i-motif structures. The i-motif is a DNA quadruplex that occurs as four stretches of cytosine repeat sequences form C·CH(+) base pairs, and their stabilization requires slightly acidic conditions. This unique property has produced the first DNA molecular motor driven by pH changes. The motor is reliable, and studies show that it is capable of millisecond running speeds, comparable to the speed of natural protein motors. With careful design, the output of these types of motors was combined to drive micrometer-sized cantilevers bend. Using established DNA nanostructure assembly and functionalization methods, researchers can easily integrate the motor within other DNA assembled structures and functional units, producing DNA molecular devices with new functions such as suprahydrophobic/suprahydrophilic smart surfaces that switch, intelligent nanopores triggered by pH changes, molecular logic gates, and DNA nanosprings. Recently, researchers have produced motors driven by light and electricity, which have allowed DNA motors to be integrated within silicon-based nanodevices. Moreover, some devices based on i-motif structures have proven useful for investigating processes within living cells. The pH-responsiveness of the i-motif structure also provides a way to control the stepwise assembly of DNA nanostructures. In addition, because of the stability of the i-motif, this structure can serve as the stem of one-dimensional nanowires, and a four-strand stem can provide a new basis for three-dimensional DNA structures such as pillars. By sacrificing some accuracy in assembly, we used these properties to prepare the first fast-responding pure DNA supramolecular hydrogel. This hydrogel does not swell and cannot encapsulate small molecules. These unique properties could lead to new developments in smart materials based on DNA assembly and support important applications in fields such as tissue engineering. We expect that DNA nanotechnology will continue to develop rapidly. At a fundamental level, further studies should lead to greater understanding of the energy transformation and material transportation mechanisms at the nanometer scale. In terms of applications, we expect that many of these elegant molecular devices will soon be used in vivo. These further studies could demonstrate the power of DNA nanotechnology in biology, material science, chemistry, and physics.

Frame‐Guided Assembly of Vesicles with Programmed Geometry and Dimensions

In molecular self-assembly molecules form organized structures or patterns. The control of the self-assembly process is an important and challenging topic. Inspired by the cytoskeletal-membrane protein lipid bilayer system that determines the shape of eukaryotic cells, we developed a frame-guided assembly process as a general strategy to prepare heterovesicles with programmed geometry and dimensions. This method offers greater control over self-assembly which may benefit the understanding of the formation mechanism as well as the functions of the cell membrane.

Thermally Triggered Frame-Guided Assembly†

We report a thermally triggered frame-guided assembly (FGA) strategy for the preparation of vesicles. We employ thermally responsive poly(propylene oxide) (PPO) to make the leading hydrophobic groups (LHGs) thermally responsive, so that they are hydrophilic below the low critical solution temperature (LCST) and the frame forms in a homogeneous environment. When the temperature is increased above the LCST, the LHGs become hydrophobic and the assembly process is triggered, which drives DNA-b-PPO to assemble around the LHGs, forming vesicles. This work verified that FGA is a general strategy and can be applied to polymeric systems. The thermally triggered assembly not only provides more controllability over the FGA process but also promotes an in-depth understanding of the FGA strategy and in a broad view, the formation mechanism and functions of cell membrane.

A brief review of methods for terminal functionalization of DNA

The functionalized DNA has been widely developed and played a more and more important role in life science and material science during last decades. Therefore, methods to effectively endue DNA new functions by modifying DNA have been developed quickly. In this review, we will give an introduction in the methods for covalent terminal functionalization of DNA, including solid-phase functionalization and solution coupling functionalization, mainly on the technical aspect. The application of these functionalized DNA will be also introduced.

Cuboid Vesicles Formed by Frame-Guided Assembly on DNA Origami Scaffolds

We describe the use of a frame-guided assembly (FGA) strategy to construct cuboid and dumbbell-shaped hetero-vesicles on DNA origami nanostructure scaffolds. These are achieved by varying the design of the DNA origami scaffolds that direct the distribution of the leading hydrophobic groups (LHG). By careful selection of LHGs, different types of amphiphiles (both polymer and small-molecule surfactants) were guided to form hetero-vesicles, demonstrating the versatility of the FGA strategy and its potential to construct asymmetric and dynamic hetero-vesicle assemblies with complex DNA nano-scaffolds.

Preparation and Self‐folding of Amphiphilic DNA Origami

Amphiphilic DNA origami is prepared by dressing multiple hydrophobic molecules on a rectangular single layer DNA origami, which is then folded or coupled in sandwich-like structures with two outer DNA origami layer and one inner hydrophobic molecules layer. The preference to form different kinds of structures could be tailored by rational design of DNA origami.

Stability study of tubular DNA origami in the presence of protein crystallisation buffer

This work offers a methodology for screening compatible buffer conditions for both DNA origami and protein crystallisation and studied how protein crystallisation buffer conditions notably cations, buffering agents, precipitants, and pH, influenced the stability of tubular DNA origami.

Using Small Molecules to Prepare Vesicles with Designable Shapes and Sizes via Frame-Guided Assembly Strategy.

Following the principle of frame-guided assembly (FGA), a small amphiphilic molecule, sodium dodecyl sulfate, is shown to form vesicles with cholesterol as the leading hydrophobic group. These findings not only demonstrate the generality of the FGA but also provide a clue to understand the formation mechanism of the cell membrane, and even the origin of life.

Tetrahedron DNA dendrimers and their encapsulation of gold nanoparticles

DNA dendrimers have achieved increasing attention recently. Previously reported DNA dendrimers used Y-DNA as monomers. Tetrahedron DNA is a rigid tetrahedral cage made of DNA. Herein, we use tetrahedron DNA as monomers to prepare tetrahedron DNA dendrimers. The prepared tetrahedron DNA dendrimers have larger size compared with those made of Y-DNA. In addition, thanks to the central cavity of tetrahedron DNA monomers, some nanoscale structures (e.g., gold nanoparticles) can be encapsulated within tetrahedron DNA monomers. Tetrahedron DNA encapsulated with gold nanoparticles can be further assembled into dendrimers, guiding gold nanoparticles into clusters.

Precisely Controlled 2D Free-Floating Nanosheets of Amphiphilic Molecules through Frame-Guided Assembly.

2D assembly of amphiphilic molecules in aqueous solution is a challenging and intriguing topic as it is normally thermodynamically unfavorable. However, through frame-guided assembly strategy and using DNA origami as the frame, monodispersed and shape-defined nanosheets are prepared. As leading hydrophobic groups (LHGs) are anchored on the frames, amphiphilic molecules in aqueous solution are guided to assemble in the hydrophobic region. By adjusting the distribution of the LHGs, the size and shape of the assemblies can be controlled precisely.