Yan Liu

• Doctor of Philosophy
• Professor (Full) at Arizona State University

Photosynthetic organisms organize discrete light‐harvesting complexes into large‐scale networks to facilitate efficient light collection and utilization. Inspired by nature, herein, synthetic DNA templates were used to direct the formation of dye aggregates with a cyanine dye, K21, into discrete branched photonic complexes, and two‐dimensional (2D)...

Photosynthetic organisms organize discrete light‐harvesting complexes into large‐scale networks to facilitate efficient light collection and utilization. Inspired by nature, herein, synthetic DNA templates were used to direct the formation of dye aggregates with a cyanine dye, K21, into discrete branched photonic complexes, and two‐dimensional (2D)...

Selection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. We show that Restricted Boltzmann Machines (RBMs), an unsupervised two-layer neural network architecture, can successfully be train...

Rationally designed photonic complexes promoting the efficient collection and harnessing of excitation energy are key to artificial photosynthesis and optoelectronics. The precise control over the geometric arrangement and energy flow of photonic materials is in great demand. Mimicking natural light-harvesting systems in terms of multi-pigment comp...

Selection protocols such as SELEX, where molecules are selected over multiple rounds for their ability to bind to a target molecule of interest, are popular methods for obtaining binders for diagnostic and therapeutic purposes. With the increasing amount of such high-throughput experimental data available, machine learning techniques have become in...

Nanophotonics is an emerging hot area that finds applications in optics, sensing and energy harvesting. Conventional fabrication methods are generally limited by their low spatial resolution and patterning capability, which cannot meet the demands of developing advanced nanophotonic structures. DNA origami has enabled a number of novel bottom-up st...

Controllable strong interactions between a nanocavity and a single emitter is important to manipulating optical emission in a nanophotonic systems but challenging to achieve. Here a three-dimensional DNA origami, named as DNA rack (DR) is proposed and demonstrated to deterministically and precisely assemble single emitters within ultra-small plasmo...

A Correction to this paper has been published: https://doi.org/10.1038/s41557-020-0539-8.

Controllable strong interactions between a nanocavity and a single emitter is important to manipulating optical emission in a nanophotonic systems but challenging to achieve. Here a three-dimensional DNA origami, named as DNA rack (DR) is proposed and demonstrated to deterministically and precisely assemble single emitters within ultra-small plasmo...

Controlling the nucleation step of a self-assembly system is essential for engineering structural complexity and dynamic behaviors. Here, we design a "frame-filling" model system that comprises one type of self-complementary DNA tile and a hosting DNA origami frame to investigate the inherent dynamics of three general nucleation modes in nucleated...

DNA origami has emerged as a highly programmable method to construct customized objects and functional devices in the 10–100 nm scale. Scaling up the size of the DNA origami would enable many potential applications, which include metamaterial construction and surface-based biophysical assays. Here we demonstrate that a six-helix bundle DNA origami...

A rhombohedral DNA crystal was self‐assembled with prescribed symmetry using a unique immobile Holliday junction sequence. The DNA scaffold contained broad solvent channels along the six‐fold axis and an arrangement of packed layers in a solvent‐excluded environment when viewed at a 90° rotation. Abstract DNA is an ideal molecule for the construct...

DNA is an ideal molecule for the construction of 3D crystals with tunable properties owing to its high programmability based on canonical Watson–Crick base pairing, with crystal assembly in all three dimensions facilitated by immobile Holliday junctions and sticky end cohesion. Despite the promise of these systems, only a handful of unique crystal...

The ability to identify single-nucleotide mutations is critical for probing cell biology and for precise detection of disease. However, the small differences in hybridization energy provided by single-base changes makes identification of these mutations challenging in living cells and complex reaction environments. Here, we report a class of de nov...

Circular dichroism (CD) from hybrid complexes of plasmonic nanostructures and chiral molecules has recently attracted significant interest. However, the hierarchical chiral self-assembly of molecules on surfaces of metal nanostructures has remained challenging. As a result, a deep understanding of plasmon-exciton coupling between surface plasmons a...

DNA nanotechnology is developed for decades to construct dynamic responsive systems in optics, quantum electronics, and therapeutics. While DNA nanotechnology is a powerful tool in nanomaterials, it is rare to see successful applications of DNA molecules in the macroscopic regime of material sciences. Here, a novel strategy to magnify the nanometer...

Multivalent aptamers that interact with target protein through multiple sites exhibit a much stronger binding strength than their monovalent counterparts. A single‐stranded DNA library that contains a predefined DNA nanostructure was used to present two random‐looped sites for bivalent aptamer evolution. Ultra‐high‐affinity bivalent aptamers with K...

Synthetic catalytic DNA circuits are important signal amplification tools for molecular programming due to their robust and modular properties. In catalytic circuits, the reactant recycling operation is essential to facilitate continuous processes. Therefore, it is desirable to develop new methods for the recycling of reactants and to improve the r...

Multivalent aptamers that interact with their target proteins through multiple sites exhibit much stronger binding strengths than their monovalent counterparts. In this work, we have designed a single‐stranded DNA (ssDNA) library (10¹⁵ molecules, each 145 nt) based on a predefined DNA nanostructure designed to present two random‐loop sites for biva...

The benzothiazole cyanine dye, K21, forms dye aggregates on double stranded DNA (dsDNA) templates. These aggregates exhibit a red-shifted absorption band, enhanced fluorescence emission and an increased fluorescence lifetime, all indicating strong excitonic coupling among the dye molecules. K21 aggregate formation on dsDNA is only weakly sequence d...

Molecular knots represent one of the most extraordinary topological structures in biological polymers. Creating highly knotted nanostructures with well-defined and sophisticated geometries and topologies remains challenging. Here, we demonstrate a general strategy to design and construct highly knotted nucleic acid nanostructures, each weaved from...

Patients with acute kidney injury (AKI) frequently require kidney transplantation and supportive therapies, such as rehydration and dialysis. Here, we show that radiolabelled DNA origami nanostructures (DONs) with rectangular, triangular and tubular shapes accumulate preferentially in the kidneys of healthy mice and mice with rhabdomyolysis-induced...

Advances in biomimetic microelectronics offer a range of patterned assemblies of proteins and cells for in vitro metabolic engineering where coordinated biochemical pathways allow cell metabolism to be characterized and potentially controlled on a chip. To achieve these goals, developing new methods for interfacing biological systems to microelectr...

DNA tile-based assembly provides a promising bottom-up avenue to create designer 2D and 3D crystalline structures that may host guest molecules or nanoparticles to achieve novel functionalities. Herein, we introduce a new kind of DNA tiles (named layered-crossover tiles) that each consists of two or four pairs of layered crossovers to bridge DNA he...

The ability to dynamically tune the self-assembled structures of nanoparticles is of significant interest in the fields of chemistry and mate-rial studies. However, it continues to be challenging to dynamically tune the chiral superstructures of nanoparticles and actively switch the chiral optical properties thereof. Here, we dynamically controlled...

Programming self‐assembled designer DNA crystals with various lattices and functions is not only the original goal of DNA nanotechnology, but also one of the most important targets for nanofabrication using nucleic acids. The resulting porous materials possess atomic precision for several potential applications that fundamentally rely on crystallin...

Programming self‐assembled designer DNA crystals with various lattices and functions is not only the original goal of DNA nanotechnology, but also one of the most important targets for nanofabrication using nucleic acids. The resulting porous materials possess atomic precision for several potential applications that fundamentally rely on crystallin...

Genetically encoded protein scaffolds often serve as templates for the mineralization of biocomposite materials with complex yet highly controlled structural features that span from nanometres to the macroscopic scale. Methods developed to mimic these fabrication capabilities can produce synthetic materials with well defined micro- and macro-sized...

Three-dimensional (3D) DNA nanostructures facilitate the directed self-assembly of various objects with designed patterns with nanometer scale addressability. Here, we report the enhancement of cytochrome c (cyt c) redox activity by using a designed 3D DNA nanostructure attached to a gold electrode to spatially control the position of cyt c within...

Substrate channeling, in which metabolic intermediate is directly passed from one enzyme to the next enzyme in an enzyme cascade, accelerates the processing of metabolites and improves substrate selectivity. Synthetic design and precise control of channeling outside the cellular environment are of significance in areas such as synthetic biology, sy...

Nanoscale robots have potential as intelligent drug delivery systems that respond to molecular triggers1,2,3,4. Using DNA origami we constructed an autonomous DNA robot programmed to transport payloads and present them specifically in tumors. Our nanorobot is functionalized on the outside with a DNA aptamer that binds nucleolin, a protein specifica...

Large origami from a single strand Nanostructures created by origami-like folding of nucleic acids are usually formed by base-pairing interactions between multiple strands. Han et al. show that large origami (up to 10,000 nucleotides for DNA and 6000 nucleotides for RNA) can be created in simple shapes, such as a rhombus or a heart. A single strand...

In living cells, compartmented or membrane-associated enzymes are often assembled into large networks for cooperatively catalyzing cascade reaction pathways essential for the cellular metabolism. Here, we report the assembly of an artificial 2D enzyme network of two cascade enzymes, glucose-6-phosphate dehydrogenase (G6PDH) and lactate dehydrogenas...

An important challenge in molecular assembly and hierarchical molecular engineering is to control and program the chiral directional self-assembly. Here, we present a versatile DNA surface adapter that can be programmed to self-assemble into various chiral supramolecular architectures, thereby regulating the chiral directional "bonding" of gold nan...

An important challenge in molecular assembly and hierarchical molecular engineering is to control and program the chiral directional self-assembly. Here, we present a versatile DNA surface adapter that can be programmed to self-assemble into various chiral supramolecular architectures, thereby regulating the chiral directional "bonding" of gold nan...

Although many models have been developed to guide the design and implementation of DNA tile-based self-assembly systems with increasing complexity, the fundamental assumptions of the models have not been thoroughly tested. To expand the quantitative understanding of DNA tile-based self-assembly and to test the fundamental assumptions of self-assemb...

The foundational goal of structural DNA nanotechnology—the field that uses oligonucleotides as a molecular building block for the programmable self-assembly of nanostructured systems—was to use DNA to construct three-dimensional (3D) lattices for solving macromolecular structures. The programmable nature of DNA makes it an ideal system for rational...

DNA has become one of the most extensively used molecular building blocks for engineering self-assembling materials. DNA origami is a technique that uses hundreds of short DNA oligonucleotides, called staple strands, to fold a long single-stranded DNA, which is called a scaffold strand, into various designer nanoscale architectures. DNA origami has...

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 amp...

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 amp...

Designer DNA architectures with nanoscale geometric controls provide a programmable molecular toolbox for engineering complex nanodevices. Scaffolded DNA origami has dramatically improved our ability to design and construct DNA nanostructures with finite size and spatial addressability. Here we report a novel design strategy to engineer multilayere...

Designer DNA architectures with nanoscale geometric controls provide a programmable molecular toolbox for engineering complex nanodevices. Scaffolded DNA origami has dramatically improved our ability to design and construct DNA nanostructures with finite size and spatial addressability. Here we report a novel design strategy to engineer multilayere...

Structural DNA nanotechnology combines branched DNA junctions with sticky-ended cohesion to create self-assembling macromolecular architectures. One of the key goals of structural DNA nanotechnology is to construct three-dimensional (3D) crystalline lattices. Here we present a new DNA motif and a strategy that has led to the assembly of a 3D lattic...

The inside cover picture shows the efficient coupling of substrate transport between enzymes, which is important for the overall activity of the pathway. This mechanism controls the depletion of intermediate molecules that drives the reaction forward. The authors thank Michael Northrop for designing the cover image. More information can be found in...

Modular DNA tile-based self-assembly is a versatile way to engineer basic tessellation patterns on the nanometer scale, but it remains challenging to achieve high levels of structural complexity. We introduce a set of general design principles to create intricate DNA tessellations by employing multi-arm DNA motifs with low symmetry. We achieved two...

Modular DNA tile-based self-assembly is a versatile way to engineer basic tessellation patterns on the nanometer scale, but it remains challenging to achieve high levels of structural complexity. We introduce a set of general design principles to create intricate DNA tessellations by employing multi-arm DNA motifs with low symmetry. We achieved two...

Artificial multi-enzyme systems with precise and dynamic control over the enzyme pathway activity are of great significance in bionanotechnology and synthetic biology. Herein, we exploit a spatially addressable DNA nanoplatform for the directional regulation of two enzyme pathways (G6pDH-MDH and G6pDH-LDH) through the control of NAD(+) substrate ch...

Artificial multi-enzyme systems with precise and dynamic control over the enzyme pathway activity are of great significance in bionanotechnology and synthetic biology. Herein, we exploit a spatially addressable DNA nanoplatform for the directional regulation of two enzyme pathways (G6pDH–MDH and G6pDH–LDH) through the control of NAD+ substrate chan...

Cascade reactions drive and regulate a variety ofmetabolic activities. Efficient coupling of substrate transport between enzymes is important for overall pathway activity, and also controls the depletion of intermediate molecules that drive the reaction forward. Here, we assembled a three-enzyme pathway on a series of DNA nanoscaffolds to investiga...

Cells routinely compartmentalize enzymes for enhanced efficiency of their metabolic pathways. Here we report a general approach to construct DNA nanocaged enzymes for enhancing catalytic activity and stability. Nanocaged enzymes are realized by self-assembly into DNA nanocages with well-controlled stoichiometry and architecture that enabled a syste...

Supplementary Figures 1-61, Supplementary Tables 1-4, Supplementary Notes 1-4, Supplementary Methods and Supplementary References

Biomolecular programming utilizes the reactions and information stored in biological molecules, such as proteins and nucleic acids, for computational purposes. DNA has proven itself an excellent candidate for building logic operating systems due to its highly predictable molecular behavior. In this work we designed and realized an XOR logic gate an...

Controlling DNA self-assembly processes using rationally designed logic gates is a major goal of DNA-based nanotechnology and programming. Such controls could facilitate the hierarchical engineering of complex nanopatterns responding to various molecular triggers or inputs. Here we demonstrate the use of a series of DNAzyme-based logic gates to con...

Structural DNA nanotechnology and the DNA origami technique, in particular, have provided a range of spatially addressable two- and three-dimensional nanostructures. These structures are, however, typically formed of tightly packed parallel helices. The development of wireframe structures should allow the creation of novel designs with unique funct...

This review focuses on how to use DNA nanostructures as scaffolds to organize biological molecules. First, we introduce the use of structural DNA nanotechnology to engineer rationally designed nanostructures. Second, we survey approaches used to generate protein-DNA conjugates. Third, we discuss studies exploring DNA scaffolds to create DNA nanodev...

DNA nanotechnology has touched the epitome of miniaturization by integrating various nanometer size particles with nanometer precision. This enticing bottom-up approach has employed small DNA tiles, large multi-dimensional polymeric structures or more recently DNA origami to organize nanoparticles of different inorganic materials, small organic mol...

The present invention provides novel barcode microstructures and methods for making and using the microstructures for molecular recognition, and/or delivery of therapeutic, diagnostic, contrast, and imaging agents.

A structurally and compositionally well-defined and spectrally tunable artificial light-harvesting system has been constructed in which multiple organic dyes attached to a 3arm DNA nanostructure serve as an antenna conjugated to a photosynthetic reaction center isolated from Rhodobacter sphaeroides 2.4.1. The light energy absorbed by the dye molecu...

The dependence of quantum dot (QD) fluorescent emission on the proximity of 30 nm gold nanoparticles (AuNPs) was studied with controlled inter-particle distances ranging from 15-70 nm. This was achieved by co-assembling DNA-conjugated QDs and AuNPs in a 1:1 ratio at precise positions on a triangular shaped DNA origami platform. A profound, long ran...

Over the last three decades DNA has emerged as an exceptional molecular building block for nano-construction due to its predictable conformation and programmable intra- and inter-molecular base pairing interactions. A variety of convenient design rules and reliable assembly methods have been developed to engineer DNA nanostructures of increasing co...

Building plasmonic nanostructures using biomolecules as scaffolds has shown great potential for attaining tunable light absorption and emission via precise spatial organization of optical species and antennae. Here we report bottom-up assembly of hierarchical plasmonic nanostructures using DNA origami templates and MS2 virus capsids. These serve as...

Proteins have evolved to carry out nearly all the work required of living organisms within complex inter- and intracellular environments. However, systematically investigating the range of interactions experienced by a protein that influence its function remains challenging. DNA nanostructures are emerging as a convenient method to arrange a broad...

Swinging arms are a key functional component of multistep catalytic transformations in many naturally occurring multi-enzyme complexes. This arm is typically a prosthetic chemical group that is covalently attached to the enzyme complex via a flexible linker, allowing the direct transfer of substrate molecules between multiple active sites within th...

Conspectus DNA nanotechnology is one of the most flourishing interdisciplinary research fields. DNA nanostructures can be designed to self-assemble into a variety of periodic or aperiodic patterns of different shapes and length scales. They can be used as scaffolds for organizing other nanoparticles, proteins, and chemical groups, leveraging their...

Investigating how individual molecular components interact with one another within DNA nano-architectures, both in terms of their spatial and temporal interactions, is fundamentally important for a better understanding of their physical behaviors. This will provide researchers with valuable insight for designing more complex higher-order structures...

Thermodynamics and Kinetics of Parallel DNA Crossovers Probed by Fӧrster Resonance Energy Transfer Angela Edwards, Alessio Andreoni, Hao Yan and Yan Liu The Department of Chemistry and Biochemistry and the Biodesign Institute, Arizona State University, Tempe, AZ 85287 (USA) Abstract Parallel crossovers are one of the two possible conformations of...

QDs that emit in the infrared (IR) range are of special interest at the moment because of their potential as tissue imaging reagents. Due to autofluorescence from tissues, QDs that emit in the visible range fail to produce good signal to noise ratios. Here we report the production of CdxPb1-xTe tertiary-alloyed QDs that emit in the 1100-1300 nm wav...

The controlled nucleation of nanoscale building blocks by geometrically defined seeds implanted in DNA nanoscaffolds represents a unique strategy to study and understand the dynamic processes of molecular self-assembly. Here we utilized a two dimensional (2D) DNA origami frame with a hol-low interior and selectively positioned DNA hybridization see...

Engineered cysteine residues near the primary electron donor (P) of the reaction center from the purple photosynthetic bacterium Rhodobacter sphaeroides were covalently conjugated to each of several dye molecules in order to explore the geometric design and spectral requirements for energy transfer between an artificial antenna system and the react...

Progress in nanosciences and life sciences is closely related to developments of high resolution imaging techniques. We introduce a technique which produces correlated topography and fluorescence lifetime images with nanometer resolution. Spot sizes below 5 nm are achieved by quenching of the fluorescence with silicon probes of an atomic force micr...

This perspective provides an overview of the techniques that have been developed for the conjugation of DNA to colloidal quantum dots (QDs), or semiconductor nanocrystals. Methods described include: ligand exchange at the QD surface, covalent conjugation of DNA to the QD surface ligands, and one-step DNA functionalization on core QDs or during core...

Scaffolded DNA origami, a versatile method to construct high yield selfassembled DNA nanostructures, has been investigated to develop water-soluble nanoarrays for label free RNA detection, drug delivery, molecular positioning and recognition, and spatially ordered catalysis of single molecule chemical reactions. Its attributes that facilitate these...

In a parallel universe: DNA origami structures based on modified parallel double-crossover tiles were constructed and a unidirectional (parallel) arrangement of the scaffold strand (gray lines) was used in the assembly of a variety of 2D and 3D DNA origami structures. This will greatly expand the diversity of DNA origami and enable their assembly i...

AbstractDNA nanotechnology utilizes synthetic DNA strands as the building material to construct nanoscale devices, and the field has developed rapidly over the past decade. Recently, the use of DNA nanostructures for various applications, particularly biomedical ones, has drawn great interest. This review focuses on the most recent research directe...

The functions of regulatory enzymes are essential to modulating cellular pathways. Here we report a tweezer-like DNA nanodevice to actuate the activity of an enzyme/cofactor pair. A dehydrogenase and NAD(+) cofactor are attached to different arms of the DNA tweezer structure and actuation of enzymatic function is achieved by switching the tweezers...

We used DNA origami as a platform to coassemble a 20 nm gold nanoparticle (AuNP) and an organic fluorophore (TAMRA) and studied the distance-dependent plasmonic interactions between the particle and the dye using steady state fluorescence and lifetime measurements. Greater fluorescence quenching was found at smaller dye-particle distances, which wa...

In bio-molecular programming, the properties of bio-molecules such as proteins and nucleic acids are harnessed for computational purposes. The field has gained considerable attention due to the possibility of exploiting the massive parallelism that is inherent in natural systems to solve computational problems. DNA has already been used to build co...

Archimedean tilings are periodic polygonal tessellations that are created by placing regular polygons edge-to-edge around a vertex to fill the plane. Archimedean tilings were first classified by Johannes Kepler in 1619 and are still of great interest today due to the unique and interesting properties of the resulting patterns. For example, Archimed...

Building controlled and tunable multiplex nanoheterostructures (NHSs) is critical for renewable energy and biosensor applications. In this paper, we demonstrate a facile and highly efficient method to functionalize one-dimensional (1D) colloidal II–VI semiconductor nanowires with a high coverage of single-stranded DNA (ssDNA) for the construction o...

Understanding the thermodynamic properties of complex DNA nanostructures, including rationally designed two dimensional (2D) and three dimensional (3D) DNA origami, facilitates more accurate spatio-temporal control and effective functionalization of the structures by other elements. In this work fluorescein and Tetramethylrhodamine (TAMRA), a Föste...

We report a scaffold-free approach in which four- and six-helix DNA bundle units, assembled from a small number of single stranded DNA oligonucleotides precisely arranged in networks of contiguous and semi-crossover strands, are connected into DNA nano rings. Nearly uniform structures with well-defined diameters of 53 ± 7 nm, 81 ± 9 nm, 85 ± 8 nm a...

Proteins and peptides fold into dynamic structures that access a broad functional landscape, however, designing artificial polypeptide systems is still a great challenge. Conversely, DNA engineering is now routinely used to build a wide variety of 2D and 3D nanostructures from hybridization based rules, and their functional diversity can be signifi...

Engineering wireframe architectures and scaffolds of increasing complexity is one of the important challenges in nanotechnology. We present a design strategy to create gridiron-like DNA structures. A series of four-arm junctions are used as vertices within a network of double-helical DNA fragments. Deliberate distortion of the junctions from their...

Achieving DNA-functionalized semiconductor quantum dots (QDs) that are robust enough to be compatible with the DNA nanotechnology that withstand precipitation at high temperature and ionic strength is a challenge. Here we report a method that facilitates the synthesis of stable core/shell (1–20 monolayers) QD-DNA conjugates in which the end part (5...

Constructing intricate geometric arrangements of components is one of the central challenges of nanotechnology. Here we report a convenient, versatile method to organize discrete length single-walled carbon nanotubes (SWNT) into complex geometries using 2D DNA origami structures. First, a size exclusion HPLC purification protocol was used to isolat...

The assembly and isolation of DNA oligonucleotide-functionalized gold nanoparticles (AuNPs) has become a well-developed technology that is based on the strong bonding interactions between gold and thiolated DNA. However, achieving DNA-functionalized semiconductor quantum dots (QDs) that are robust enough to withstand precipitation at high temperatu...

In this paper, a power and area efficient charge-pump phase-locked loop (CPPLL) is proposed. The design utilizes a top-down methodology to determine system parameters. The PLL is implemented in 0.18μm CMOS technology and its supply voltage is 1.8V. The PLL has in input clock frequency of 25MHz and an output clock frequency of 0.8-1.6GHz with 50μm*1...

Scaffolded DNA origami is a widely used technology for self-assembling precisely structured nanoscale objects that contain a large number of addressable features. Typical scaffolds are long, single strands of DNA (ssDNA) that are folded into distinct shapes through the action of many, short ssDNA staples that are complementary to several different...

Safe and effective vaccines offer the best intervention for disease control. One strategy to maximize vaccine immunogenicity without compromising safety is to rationally design molecular complexes that mimic the natural structure of immunogenic microbes but without the disease-causing components. Here we use highly programmable DNA nanostructures a...