DNA is traditionally known as a central genetic biomolecule in living systems. From an alternative perspective, DNA is a versatile molecular building-block for the construction of functional materials, in particular biomaterials, due to its intrinsic biological attributes, molecular recognition capability, sequence programmability, and biocompatibility. The topologies of DNA building-blocks mainly include linear, circular, and branched types. Branched DNA recently has been extensively employed as a versatile building-block to synthesize new biomaterials, and an assortment of promising applications have been explored. In this review, we discuss the progress on DNA functional materials assembled from branched DNA. We first briefly introduce the background information on DNA molecules and sketch the development history of DNA functional materials constructed from branched DNA. In the second part, the synthetic strategies of branched DNA as building-blocks are categorized into base-pairing assembly and chemical bonding. In the third part, construction strategies for the branched DNA-based functional materials are comprehensively summarized including tile-mediated assembly, DNA origami, dynamic assembly, and hybrid assembly. In the fourth part, applications including diagnostics, protein engineering, drug and gene delivery, therapeutics, and cell engineering are demonstrated. In the end, an insight into the challenges and future perspectives is provided. We envision that branched DNA functional materials can not only enrich the DNA nanotechnology by ingenious design and synthesis but also promote the development of interdisciplinary fields in chemistry, biology, medicine, and engineering, ultimately addressing the growing demands on biological and medical-related applications in the real world.

DNA Functional Materials Assembled from Branched DNA: Design, Synthesis, and Applications.

The article discusses molecular recognition and overviews the key concepts -storage and retrieval of chemical information by molecular structures, supramolecular reagents and catalysts, molecular transport, semiochemistry and self assembly. The prospects of controlling supramolecular architecture through engineered molecular recognition and design of ‘programmed systems’ controlled by molecular information are also discussed.

Supramolecular chemistry

DNA encodes the genetic information; recently, it has also become a key player in material science. Given the specific Watson-Crick base-pairing interactions between only four types of nucleotides, well-designed DNA self-assembly can be programmable and predictable. Stem-loops, sticky ends, Holliday junctions, DNA tiles, and lattices are typical motifs for forming DNA-based structures. The oligonucleotides experience thermal annealing in a near-neutral buffer containing a divalent cation (usually Mg2+ ) to produce a variety of DNA nanostructures. These structures not only show beautiful landscape, but can also be endowed with multifaceted functionalities. This Review begins with the fundamental characterization and evolutionary trajectory of DNA-based artificial structures, but concentrates on their biomedical applications. The coverage spans from controlled drug delivery to high therapeutic profile and accurate diagnosis. A variety of DNA-based materials, including aptamers, hydrogels, origamis, and tetrahedrons, are widely utilized in different biomedical fields. In addition, to achieve better performance and functionality, material hybridization is widely witnessed, and DNA nanostructure modification is also discussed. Although there are impressive advances and high expectations, the development of DNA-based structures/technologies is still hindered by several commonly recognized challenges, such as nuclease instability, lack of pharmacokinetics data, and relatively high synthesis cost.

Programmable and Multifunctional DNA-Based Materials for Biomedical Applications

Design of logic gates using spiking neural P systems with homogeneous neurons and astrocytes-like control

Spiking neural P systems with rules on synapses

DNA strand displacement technology performs well in sensing and programming DNA segments. In this work, we construct DNA molecular systems based on DNA strand displacement performing computation of logic gates. Specifically, a class of so-called “DNA neurons” are achieved, in which a “smart” way inspired by biological neurons encoding information is developed to encode and deliver information using DNA molecules. The “DNA neuron” is bistable, that is, it can sense DNA molecules as input signals, and release “negative” or “positive” signals DNA molecules. We design intelligent DNA molecular systems that are constructed by cascading some particularly organized “DNA neurons”, which could perform logic computation, including AND, OR, XOR logic gates, automatically. Both simulation results using visual DSD (DNA strand displacement) software and experimental results are obtained, which shows that the proposed systems can detect DNA signals with high sensitivity and accretion; moreover, the systems can process input signals automatically with complex nonlinear logic. The method proposed in this work may provide a new way to construct a sensitive molecular signal detection system with neurons spiking behavior in vitro, and can be used to develop intelligent molecular processing systems in vivo.

/pdf/a-novel-bio-sensor-based-on-dna-strand-displacement-5zoi0us38u.pdf

A novel bio-sensor based on DNA strand displacement.

DNA tile based self-assembly provides a bottom-up approach to construct desired nanostructures. DNA tiles have been directly constructed from ssDNA and readily self-assembled into 2D lattices and 3D superstructures. However, for more complex lattice designs including algorithmic assemblies requiring larger tile sets, a more modular approach could prove useful. This paper reports a new DNA 'sub-tile' strategy to easily create whole families of programmable tiles. Here, we demonstrate the stability and flexibility of our sub-tile structures by constructing 3-, 4- and 6-arm DNA tiles that are subsequently assembled into 2D lattices and 3D nanotubes according to a hierarchical design. Assembly of sub-tiles, tiles, and superstructures was analyzed using polyacrylamide gel electrophoresis and atomic force microscopy. DNA tile self-assembly methods provide a bottom-up approach to create desired nanostructures; the sub-tile strategy adds a useful new layer to this technique. Complex units can be made from simple parts. The sub-tile approach enables the rapid redesign and prototyping of complex DNA tile sets and tiles with asymmetric designs.

Programmable DNA tile self-assembly using a hierarchical sub-tile strategy.

National Natural Science Foundation of China [61202011, 61033003, 91130034, 30870826]; Ph.D. Programs Foundation of Ministry of Education of China [20100142110072]; Fundamental Research Funds for the Central Universities [2010ZD001, 2010MS003]; National Science Foundation of Hubei Province [2008CDB113, 2011CDA027]

Small Universal Spiking Neural P Systems with Anti-Spikes

The design of DNA nanotubes is a promising and hot research branch in structural DNA nanotechnology, which is rapidly developing as a versatile method for achieving subtle nanometer scale materials and molecular diagnostic/curative devices. Multifarious methods have been proposed to achieve varied DNA nanotubes, such as using square tiles and single-stranded tiles, but it is still a challenge to develop a bottom-up assembly way to build DNA nanotubes with different diameters and patterns using certain universal DNA nanostructures. This work addresses the challenge by assembling three types of spatial DNA nanotubes with different diameters and patterns from the so-called "basic bricks", i.e., hierarchical DNA sub-tiles. A high processing rate and throughput synthesis of DNA nanotubes are observed and analyzed by atomic force microscopy. Experimental observations and data analysis suggests the stability and controllability of DNA nanotubes assembled by hierarchical DNA sub-tiles.

Construction of DNA nanotubes with controllable diameters and patterns using hierarchical DNA sub-tiles

School of Computer and Information, Anqing Normal University, Anqing 246133, Anhui, ChinaMembrane computing is a new branch of natural computing whose aim is to abstract computingideas from the structure and the functioning of living cells, as well as from the cell cooperationin tissues, populations of cells and the brain. The obtained models are called P systems. Theresearch in this area developed very fast, both towards theory, such as Turing computability, lan-guage and automata theory (e.g., characterizations of Turing completeness), computational efﬁ-ciency (polynomial solutions to NP-complete problems by trading off time to space) and applications(in system biology, bio-medicine, computer graphics, approximate optimization, robot control, cryp-tography, ecology and economics modeling, etc.). There are three main classes of P systems: (1)cell-like P systems inspired from living cells, (2) tissue-like P systems inspired from tissues, and(3) neural-like P systems inspired from neural systems. In this paper, we brieﬂy introduce cell-likeand tissue-like P systems, and then discuss a class of neural-like P systems, called spiking neuralP systems, in details: the formal deﬁnition of the system is ﬁrstly introduced, and some results ofthe systems are recalled in two aspects: computational completeness and computational efﬁciency.

https://www.researchgate.net/profile/Tao_Song11/publication/272273093_An_Overview_of_Membrane_Computing/links/5512046d0cf270fd7e31c4b8.pdf

Xiaolong Shi

Papers

A novel bio-sensor based on DNA strand displacement.

Programmable DNA tile self-assembly using a hierarchical sub-tile strategy.

Small Universal Spiking Neural P Systems with Anti-Spikes

Construction of DNA nanotubes with controllable diameters and patterns using hierarchical DNA sub-tiles

An Overview of Membrane Computing