Review Of Dna Nanotechnology Biology Essay


Nanotechnology has already become more and more significant based on the research of nanostructure application. DNA has been applied to build diverse nanostructures since it's one of the most important biomacromolecules. Presently, DNA nanotechnology becomes the most active research area in molecular biology and nanoscience. It provided a new technology, new approach for creation of nanodevice, and playing an important role in research of electronic units on molecular level.

Nanotechnology is to building a certain structural and functional molecules or even super-molecular technology based on some of the materials having a nano-scale basis. The physical level of objects involved in the nano-scale space is a relatively independent field, neither macroscopy nor microscopy, labeled as mesoscopy. It manipulates molecules and atoms on nano-scale to process materials and productions with specific function. DNA nanotechnology is a new technical subject need to grasp the law of motion and properties of atoms and molecules. It is the combination of modern science (chaotic physics, quantum mechanics, mesoscopic physics, molecular biology) and modern techniques (computer technique, micro-electronics, scanning tunneling microscopy).

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Biomacromolecules has complex structures, thus has high selectivity and non-covalently interaction in biological system. DNA is the basic genetic material in most organisms. The biochemical property and structural morphology of DNA molecules is adequate researched after the double helix structure model was presented by Waston and Crick. DNA nanotechnology is the nanotechnology based on physicochemical property of DNA molecules, generally used on molecular assembly to produce functional assembly aggregate. The base properties, constancy and specificity of base complementary laws, diversity of genetic information, particularity of conformation and targeting property of topology in reproduction process of DNA are the foundational design principles of nanotechnology. DNA itself has stable physicochemical properties and particular structure such as double helix, triplex, holliday structure and polyhedron structure. In addition, the spatial conformation, thermodynamics, nuclear and electron dynamics of DNA molecules can improve remote teleportation [1], such properties make DNA become ideal functional materials of nano-wire and nanometer devices. The double helix and its topological structure can use to be scaffold materials and models to guide assembly of functional nanocomponents for the produce of molecular-scale electronic devices [2-3]. Therefore, research of DNA nanotechnology is significant not only in life science field but also in nanomaterial field.

Method of Nano design

Top-Down approaches

Generally, Top-Down method is to prepare nanostructure from large-scale (from μm to cm) through various etching techniques which collectively called Nano etching technology. Its basic principle is to put the single nanostructure unit onto specific position of pattern to form ordering two-dimensional or three-dimensional structure in the process of nano-preparation. Therefore pattern design can process on the substrate's surface. As the development of the scanning probe microscopy technique, the nano etching technology based on STM and AFM become to an active research field presently because of its practicability and simplicity. Recently, the main etching technology divided into two different parts: CDDPN based on AFM, such as needle promote reaction, dip pen inscription [4]; etching technique based on STM, such as single molecular processing, needle tip with electrochemistry etch and field induced desorption [5]. Compare the huge advantages of these CDDPN technology on high precision and high resolution, lack of continuity and low yield are the critical defect of nanoetching technology. Presently, some improvement including automatic operation [6] or the application of parallel probe [7] are used to overcome the defect for preparation of numerous ordering nanostructures with high quality.

Using "Top-Down" method can not only prepare various three-dimensional structures, but also used to prepare porous material inherited the original topography. For example, professor M.Y.Han from University of Singapore obtained porous structure of CdO inherited original CdCO3 morphology [8] through solid phase preparation of Top-Down.

Bottom-Up approaches

Researchers called the self-assembly of simple, small structural unit, such as atom, molecule, nanoparticle, to form relatively large, complex structural system on nano-scale through weak interaction as Bottom-Up approach.

Self-assembly is a method for spontaneous organizing different ordering pattern structure using small structural unit through various interaction without human intervention. Nanostructure assembly system can be divided into two different parts: artificial nanostructure assembly system and self-assembly system. The most significant driving force in self-assembly system is the interaction between subunits, especially some non-covalent effects. For instance, use hydrogen bond, Van der Waals' force, weak ionic bond, molecular interaction energy, macroscopic interaction energy, hydrophobic interaction and hydrophilic interaction to connect substance units on nano-scale to form nanostructure assembly system.

Research and Applications

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DNA used on Nanoparticle assembly

The assembly of nanocluster and nanoparticle is the key step in the process of the nanomaterial application. The approaches of supermolecular chemical assembly could be divided into two different parts. One is Colloidal crystal method and template method. Single molecular template method is most researched and most mature method. The rigorous molecular recognition function between biomolecules result it as a promising assembly model. Moreover, it's possible to precisely control the structure, size and shape of producing particle with biomolecule model to obtain different nanocluster assembly.

Research of supermolecular aggregate assembly based on Colloidal gold combined with DNA using DNA molecules as the backbone of spatial arrangement device has already become a significant study in DNA technology. Mirkin etc [9]. make 13nm Colloidal metal particles absorb onto DNA molecule by introducing reducing drainage base at the terminus of two uncomplimentary. Design a DNA connexin containing double chains area and single chain area with two cohesive terminuses. The cohesive terminus area is complementary with two ODN. When DNA double chains molecules put into solution of ODN with Au colloidal nanoparticles, it will trigger the aggregation and precipitation of DNA colloidal substances. Temperature dependence of ultraviolet absorption spectrum changes proved the reversibility of the reaction. Because of aggregate contain big amounts of DNA molecules, the ordering of aggregation and three-dimensional structure could be identified by electron microscope. Closely assembled together in a single layer, a two-dimensional colloidal aggregate is composed by 6 nm uniform particle dispersion system. Cause DNA has improved and rigorous molecular recognition function, the assembly process has high selectivity. The biomolecules thermal instability make DNA molecules be destroy when the assembled nanoclusters reached a high temperature. In addition, because of driven assembly power comes from the nanoclusters outsourcing deposited molecules molecular recognition, thus the assembly will be possible to use this method to achieve different types and particle size of nanoclusters, which has potential applications in the preparation of the special nature and requirements of nanodevices.

DNA use as a template to prepare molecular wires

DNA molecule having a certain scale and rigidity, Single-stranded DNA molecule can in mutual non-covalent bind by base complementary effect with many different confirmations. DNA or ODN can self-assembly to form a regular two-dimensional or three-dimensional nano-network [10]. In addition, it is a powerful tool in biotechnology to control structure of DNA through design DNA base sequence and the concentration of the solution. A large number of research results show that the DNA is the most promising application of macromolecular in the field of nanoelectronics. Maeda etc. [11] make gold particles assembled into two-dimensional DNA nanotechnology network for preparation of DNA-based molecular storage and memory devices. Gold particles were ordered arrangement, the distance between adjacent approximately 260 nm. If the DNA network structure is fabricated on a silicon chip, it can be applied to the semiconductor device [12]. The use of different types of DNA free adsorption and the electric field induced in the highly ordered pyrolytic graphite surface adsorption obtain network structure of nanocrystals of different morphologies.

Monson and Woolley [13] make the copper deposited onto the substrate surface adsorbed to λDNA,prepared similar nano-wire structure with height of about 3nm. Firstly, the λDNA molecule is adsorbed on the surface of the silicon substrate and stretched. Then treated with the solution of Cu(NO3)2. When Cu(II) electrostatic adsorption to DNA Chain, then reduce with the ascorbic acid. Thus form a layer of metal shell on the surface of the DNA molecule. Such nanostructures were characterized by atomic force microscopy, therefore, the more the number of processing, DNA surface metal layer is more dense. Because of copper nanowires can be used as a cable in the nanometer integrated circuits, thus synthesis of copper wire on DNA template in the field of nanotechnology is a meaningful progress and laid the foundation for the production of functional electronic devices such as electronic switches and dipole.

Use of metal atoms in the DNA surface coverage cultivate, silver[14], gold[15], platinum[16] and palladium[17] and other metals can obtain corresponding nanowires by DNA molecules. In the research of Braun etc. [18] DNA molecule is connected in between the two gold electrodes, using DNA molecule as template, exchange a layer of silver ions on its surface and then reduce the silver ions to elemental silver, obtain a silver nanowires with 12 μm long and 100 nm diameter. Clearly, this approach would completely destroy the biological activity of the DNA molecule, and the mechanical strength of connecting wire formed by nanoparticles is poor. Devices could be formed by active DNA molecules firstly, and then start conductive processing and packaging. Lee etc. [19] found DNA could absorb the Zn2+, Ni2+, Co2+ metal ion into its double helix central area maintaining high stability and has high selectivity, thus obtain new DNA electric conductor. Rakitin etc. [20] use metal ion exchange the hydrogen atom in each base pair found that the changed DNA molecule has metal electrical conductivity and keep the biological activity of DNA molecules.

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It is a huge challenge for how to prepare high ordering nanowire or nanotube array which related to how to assembly the nanocomponents into specific functional device. Z.X. Deng develop a molecular combing technology used on alignment of one-dimensional DNA molecules. It use flow physical function formed by compressed air to make alignment of DNA molecule on surface of mica plate come true. Study found it could control the affinity between DNA molecule and surface of mica plate by adjusting the concentration of Mg2+ in solution. Using electroless deposition technology metallizing such DNA sample, research successfully prepare one-dimensional or two-dimensional orientation ordered metal nanowire array.

Because of the thickness of metal wire is more than ten times bigger than DNA template, DNA lost its evaluation information of self-structure in the process of metallization and most of production are linear structures which is not enough for the complex structural system in practical application. Z.X.Deng [21] invent an approach of molecular etching method using an artificial design DNA nanostructure as molecular mask try to etch the pattern formed by DNA chains on to surface of metal film for graphical rendering on supermolecular level. Because it could design various one-dimensional and two-dimensional DNA pattern, thus such technics could be applied on high-density storage, sensor, high-resolution display panel and nanoelectronic production fields.

Application of DNA polymorphism in nanotechnology

DNA bases normally complementary paired to form double helix base on Watson-Crick rule, but also mismatching inevitably in some situations results some special structures which also play a significant role in DNA nanotechnology. For example, two DNA chains containing G-G mismatching formed guanine quartet, thus make two helix chains come together. If there's more than one G-G mismatching on same chain may form chain guanine quartets which fold the helix chains. The change on helix structure and morphology is reversible through adsorption or release of the specific cation to adjust. The contractile property of DNA molecules can use to design new DNA molecular motor.

Bukanov etc. [22] of Boston university biomedical engineering institute research a PD-loop using a section of PNA opener to open subregion of DNA double helix. It's complementary with one chain and specific binding with ODN to form specific structure of PD-loop containing PNA, ODN and DNA. It can obtain a better superiority than amplified by PCR technology without need of integrated biological creativity when continue the circulation of process. PNA increase specificity of combination between ODN and DNA to avoid the mismatching in production of PCR. The PD-loop makes it possible to separate the particular DNA fragment from complex DNA mixture. Its specific structure could be used to build nanodevice.

Base on the controllability and predictability of interaction between DNA chains, DNA could form other structures different from standard double helix. For instance, there's 4N possibility of arrangement of cohesive terminus containing one N bases. Such huge variability and specificity of DNA base pairs give the possibility for scientists to connect the DNA chains by particular way to form needed macromolecules for nanodevice. For example, the devices begin to work when DNA structure changed. One of the disadvantages is DNA components must prepare in water solution.

Rothemund [23] from California Institute of Technology obtain bigger and more complex DNA nanostructures than ever before by ignoring the base sequence, chain purity and concentration ratio of chain in design of DNA structure. Firstly, fold DNA long chain into any shape, then use hundreds of DNA "staples" to fix folded DNA chain to form two-dimensional structure. The whole process form by self-assembly. Such research put forward the DNA nanotechnology from study to application. Rothemund named this new technique as DNA origami which could be used to build nanochemical factory or molecular electronics in the future.

4.DNA self-assembly of two-dimensional nanostructure

In recent years, controllable preparation technology of nanomaterial, such as morphology, particle size, size distribution, make huge development [24]. However, research about preparation technology, especially from uncertain and unordered nanostructure to certain and ordering nanostructure, is still priority in the field. DNA self-assembly has advantages of predictable and programmable properties. Moreover, DNA double helix has good rigidity (rigid length can reach 50 nm), length of helix (3.4 nm for 10.5 base pairs) and base sequence (A-T and C-G base pair) can be precisely controlled through base number to decide the self-assembly of double helix. Therefore, DNA structure is an ideal nano controller for aggregation morphology of nanoparticle.

It is important to lead the nanoparticle ordering arrangement on nanoscale using nanostructure from DNA self-assembly as support to build multicomponent and multifunctional nanostructure. For instance, it can use in interaction between nanoparticle on nanoscale in fundamental research, and use as new biological sensor and drug transport system in application field.

Mao, etc. [25] used roll ring polymerization approach to synthesis long one-dimensional DNA template. Such template has same sequence with single DNA chain to obtain linear array of gold nanoparticle through hybridization of gold nanoparticle with single DNA modification. Alivisatos, etc. [26] obtain different two-dimensional structure of gold nanoparticle using DNA as self-assembly template to build simple nanostructure. Kiehl, etc. [27] obtain ordering two-dimensional array of gold nanoparticle using two steps method. Yan's lab [28] introduced gold nanoparticle with DNA modification to obtain preparation of two-dimensional plane structure with one-step process. This approach successfully simplified the self-assembly process of nanostructure. In research, they found stability of nanoparticle in high salt concentration improved through T5 sequence modification on surface of gold nanoparticle. Such find is significant for more complicated self-assembly of nanostructure. Recently, Yan [29] achieved two-dimensional ordering self-assembly of quantum dot using DNA array as template. Sleiman, etc. [30] obtain planar annular structure composed with six gold nanoparticles through using vertex organic molecules to control the self-assembly process of DNA.

The discrete nanostructure has same component and shape size, its intrinsic characteristics of single unit are same as its group effects of macroscopic bulk phase. Therefore, discrete nanostructure can be an ideal model for quantitative study of interaction of photoelectric transfer properties between different nanoparticles. The physical and chemical properties presented by existence and damage morphology of discrete nanostructure can apply on new sensor technology with super-high detection sensitivity. Scientists continuous research how to build discrete structure for nanoparticle in recent years. Alivistos, etc.[31] first reported in 2004 about two-dimensional discrete nanostructure built by series gold nanoparticle and quantum dot through DNA self-assembly.

The ordering arrangement of protein on nano-scale is also an important study area. It can be a new approach for quantitative research of interaction between different proteins. Similarly, the ordering arrangement of protein can be introduced by DNA self-assembly. Park, etc.[32] obtain two-dimensional array of streptavidin using two kinds of DNA elementary programming self-assembly. Configuration density of streptavidin achieved through changing modified DNA elementary molar ratio of biotin. Yan, etc.[33] first time confirmed using aptamer to make thrombin protein ordering arrangement in linear triple helix array. Chhabra, etc. arbitrary changed position of aptamer of anti-thrombin on DNA support to obtain various thrombin protein array. Seeing new teaching ideas of phenomenon of multiple bond combination in biology, recently Yan found aptamer combined with thrombin through double bond using DNA support can obtain more stable structure. To make double bond structure between thrombin and aptamer come true, there must be a proper distance between them.

DNA nanomechanical devices

There're two basic designs of DNA nanometer devices: one is to obtain the change of atom position by using tautomerization of secondary structure of DNA; the other is to obtain the interconversion of different situations through DNA hybridization and denaturation base on Watson Crick complementary rule. Seeman and other researchers from New York University has designed three-arm, four-arm and multi-double helix armed DNA template of DNA juctions, double-crossover motifs, triple-crossover motifs. In recent study, Seeman [34] successfully design a nanometer device which can prepare different production base on DNA sequence. This is the first translation system based on rotary nanometer device which could translate one kind of information into other ones for DNA sequence translation. Therefore, it could use as a nanofactory to assembly different materials for aggregate design, information storage or input equipment of DNA computer. Seeman said "this is the big progress of material structure control on nano-scale, and finally prepare the aggregate and new materials with huge diversity and new specific properties". It is opening a new development of DNA nanotechnology.

La bean etc. [35] from Duke University use the rigid material formed by DNA multi-layers chain to build nanotube. Such nanotube could roll up into a nanometer electronic device. Cubic cross piece is a kind of material with tubular structure formed in suitable chemical condition through self-assembly. It has 25 nm diameter and 20 μm structure. Such tube is a progress in nanoline self-assembly. They can locate on specific position on large scale structure and change into wire through metallization. Programmable DNA nanostructure of self-assembly wire can allocate the components of molecular electronic device. One of the advantages of DNA self-assembly is that it can create millions of copies for same structure, it's related to the intrinsic parallelism of molecular process. Researchers considered such nanotube is suitable for mutual contact of molecule scale components of device in traditional phototypography.

It is easier to build nanometer device if there's a micro tweezer which can combine molecules or atoms optionally. Scientists from Bells Lab and Oxford University prepare a nano-scale DNA tweezers through DNA self-assembly principle based on spontaneous chemical reaction which can self-assembly. The opening and closing of tweezers is like the basic state of "0" and "1" in computer which indicate that the electronic circuit on molecule scale will appear in the near future to displace the modern silicon chip make the computer smaller and faster. At the moment such tweezers can't use in preparation of nanometer device because of big amount of problems such as how to use it to vise molecules and atoms.

Application of DNA three-dimensional structure

The building property of DNA folding make DNA backbone chain can arrange into regular lattice structure, which ordering contain more than one biological macromolecules maintaining specific sequence. It includes regular crystal structure that couldn't be formed independently, such as protein, then synthesis the crystal for crystallography experiment. Scientist predicate three-dimensional structure of the containing molecule through x-ray crystal imaging technique, which is the critical step in drug design theory, because drug molecules must tightly connect with specific position of target molecules. DNA nanotechnology is a possible solution for numbers of good acceptor molecules of drug targets which can't be sufficiently researched in traditional crystallography field.

Yan, etc. reported they obtained three-dimensional tube structure of gold nanoparticle in process of DNA self-assembly. It can selectively obtain single helix, double helix and nested helix through controlling size of gold nanoparticle. Recently, Alivisatos group also reported three-dimensional gold nanoparticle.

Turberfield and Goodman[36] found a method to aggregate into a DNA pyramid in seconds. They heat the DNA double helix chains immersed in the salt solution to the temperature just below the boiling point, then cool down rapidly. As a result, the helix formed a tetrahedron. The research group can also use singe DNA helix to connect different tetrahedrons to form bigger three-dimensional structures. These structures could be used as components to build molecule device, such as backbone of electronic circuit and delivery container of small drug.

Application of DNA nanotechnology on medicine

Gene therapy is a huge progress in therapeutics. It imported the functional genes or other therapeutic genes into patient's body through gene transduction way on genetic level to give disease resistance for patient. Efficient genetic transport and genetic expression is the key to decide whether the therapy would be success. The genetic mistakes can be removed or producing therapeutic factors, such as polypeptides, proteins, and antigens, after insert plasmid DNA into target cell. DNA could be located at cell through active targeted effect using nanotechnology: concentrated the plasmid DNA (2-300 kb) to 50-200 nm size with negative electrons resulted effective cell invasion; the size and structure of plasmid DNA nanoparticle decided whether it can be inserted onto exact binding site of nuclear DNA. Because the nanoparticle here is composed with DNA itself, thus it can also prepare the nanoparticle with both the DNA molecules and genetic vectors, such as one of recent researches--DNA nanoparticles of chitosan. The physical properties related to DNA nanoparticles still need more studies.

Concluding Remarks

This article has discussed the design method, assembly technique and modern application of DNA nanotechnology. The DNA is not only the code of life. Because modern biochemical technology and DNA synthetic technique can be conveniently controlled and programmable, it is also the universal units to produce nanomechanical structure and device. In recent years, DNA nanotechnology becomes the most active research area in molecular biology and nanoscience. It provided a new technology, new approach for creation of nanodevice, and playing an important role in research of electronic units on molecular level, quantum nanodevice, DNA computer, nano-biological machine, biological chip, nano-network, genetic therapy and study of drug mechanism. DNA nanotechnology becomes a very vitality of the scientific frontier in biochemistry which bring huge economic benefits and will trigger the technical progress in relative field.

DNA structure is attractive on application of nanomedicine with big challenges. Even if we resolve building and functional problems of DNA nanostructure, there're still some challenges for application. For example, how to resolve loading and transport problem of biological macromolecule with biological motor, and how to successfully build DNA nanostructure in human body are still need to study in the future. Moreover, it's critical about whether a DNA nanostructure could maintain correct confirmation under the physiological environment.

A significant objective of DNA nanotechnology is to assemble DNA components into frame structure which is the first step of the preparation of nano-robot with complex movement and multiple structural states for chemical assembly line. To make these objects come ture, the DNA needs to use as programmable components for design. But no matter crystallography or nano microelectronics technology cannot only rely on DNA molecules. For example, nanometal particles, nano carbon cube or other nano microelectronic components must connect with DNA molecules in specific reaction system and solution condition, and coordinate with both DNA and other compositions. Considering the complex chemical properties of such molecules, it is difficult to make this objective come true. Although scientist set up the nano microelectronics through DNA self-assembly, nanomechanics still need a more complex way for interaction with macroscopic world than adding in solution and replacing regulatory fragments. Therefore, there's a long way from lab research to development of industrialization though the study of DNA nanotechnology has already achieved some important goals.