DNA walker

Last updated

A DNA walker is a class of nucleic acid nanomachines where a nucleic acid "walker" is able to move along a nucleic acid "track". The concept of a DNA walker was first defined and named by John H. Reif in 2003. [1] A nonautonomous DNA walker requires external changes for each step, whereas an autonomous DNA walker progresses without any external changes. Various nonautonomous DNA walkers were developed, for example Shin [2] controlled the motion of DNA walker by using 'control strands' which needed to be manually added in a specific order according to the template's sequence in order to get the desired path of motion. In 2004 the first autonomous DNA walker, which did not require external changes for each step, was experimentally demonstrated by the Reif group. [3]

Contents

DNA walkers have functional properties such as a range of motion extending from linear to 2 and 3-dimensional, the ability to pick up and drop off molecular cargo, [4] performing DNA-templated synthesis, and increased velocity of motion. DNA walkers have potential applications ranging from nanomedicine to nanorobotics. [5] [6] [7] Many different fuel options have been studied including DNA hybridization, hydrolysis of DNA or ATP, and light. [8] [9] The DNA walker's function is similar to that of the proteins dynein and kinesin. [5]

Role in DNA nanotechnology

Finding a suitable nanoscale motor capable of autonomous, unidirectional, linear motion is considered important to the development of DNA nanotechnology. [5] [6] The walkers have been shown to be capable of autonomous motion over linear, 2-dimensional and 3-dimensional DNA 'tracks' through a large number of schemes. In July 2005, Bath et al. showed that another way to control DNA walker motion is to use restriction enzymes to strategically cleave the 'track', causing the forward motion of the walkers. [10] In 2010, two different sets of researchers exhibited the walkers' more complex abilities to selectively pick up and drop off molecular cargo [11] [12] and to perform DNA-templated synthesis as the walker moves along the track. [13] In late 2015, Yehl et al. showed that three orders of magnitude higher than the speeds of motion seen previously were possible when using DNA-coated spherical particles that would "roll" on a surface modified with RNA complementary to the nanoparticle's DNA. RNase H was used to hydrolyse the RNA, releasing the bound DNA and allowing the DNA to hybridize to RNA further downstream. [14] In 2018, Valero et al. described a DNA walker based on two interlocked, catenated circular double-stranded DNAs (dsDNAs) and an engineered T7 RNA polymerase (T7RNAP) firmly attached to one of the DNA circles. [15] This stator-ring unidirectionally rotated the interlocked rotor-ring by rolling circle transcription (RCT), driven by nucleotide triphosphate (NTP) hydrolysis, thereby constituting a catenated DNA wheel motor. The wheel motor produces long, repetitive RNA transcripts that remain attached to the DNA-catenane and are used to guide its directional walking along predefined ssDNA tracks arranged on a DNA nanotube.

Applications

The applications of DNA walkers include nanomedicine, [16] diagnostic sensing of biological samples, [17] nanorobotics [18] and much more. [7] In late 2015, Yehl et al. improved the DNA walker's function by increasing its velocity, and it has been proposed as the basis for a low-cost, low-tech diagnostics machine capable of detecting single nucleotide mutations and heavy-metal contamination in water. [17] In 2018 Nils Walter and his team designed a DNA walker that is capable of moving at a speed of 300 nanometres per minute. This is an order of magnitude faster than the pace of other types of DNA walker. [19]

See also

Related Research Articles

Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials.

<span class="mw-page-title-main">DNA computing</span> Computing using molecular biology hardware

DNA computing is an emerging branch of unconventional computing which uses DNA, biochemistry, and molecular biology hardware, instead of the traditional electronic computing. Research and development in this area concerns theory, experiments, and applications of DNA computing. Although the field originally started with the demonstration of a computing application by Len Adleman in 1994, it has now been expanded to several other avenues such as the development of storage technologies, nanoscale imaging modalities, synthetic controllers and reaction networks, etc.

<span class="mw-page-title-main">Nanopore sequencing</span> DNA / RNA sequencing technique

Nanopore sequencing is a third generation approach used in the sequencing of biopolymers — specifically, polynucleotides in the form of DNA or RNA.

<span class="mw-page-title-main">Nanorobotics</span> Emerging technology field

Nanoid robotics, or for short, nanorobotics or nanobotics, is an emerging technology field creating machines or robots, which are called nanorobots or simply nanobots, whose components are at or near the scale of a nanometer. More specifically, nanorobotics refers to the nanotechnology engineering discipline of designing and building nanorobots with devices ranging in size from 0.1 to 10 micrometres and constructed of nanoscale or molecular components. The terms nanobot, nanoid, nanite, nanomachine and nanomite have also been used to describe such devices currently under research and development.

<span class="mw-page-title-main">Nanomotor</span> Molecular device capable of converting energy into movement

A nanomotor is a molecular or nanoscale device capable of converting energy into movement. It can typically generate forces on the order of piconewtons.

<span class="mw-page-title-main">Molecular knot</span> Molecule whose structure resembles a knot

In chemistry, a molecular knot is a mechanically interlocked molecular architecture that is analogous to a macroscopic knot. Naturally-forming molecular knots are found in organic molecules like DNA, RNA, and proteins. It is not certain that naturally occurring knots are evolutionarily advantageous to nucleic acids or proteins, though knotting is thought to play a role in the structure, stability, and function of knotted biological molecules. The mechanism by which knots naturally form in molecules, and the mechanism by which a molecule is stabilized or improved by knotting, is ambiguous. The study of molecular knots involves the formation and applications of both naturally occurring and chemically synthesized molecular knots. Applying chemical topology and knot theory to molecular knots allows biologists to better understand the structures and synthesis of knotted organic molecules.

<span class="mw-page-title-main">Molecular machine</span> Molecular-scale artificial or biological device

Molecular machines are a class of molecules typically described as an assembly of a discrete number of molecular components intended to produce mechanical movements in response to specific stimuli, mimicking macromolecular devices such as switches and motors. Naturally occurring or biological molecular machines are responsible for vital living processes such as DNA replication and ATP synthesis. Kinesins and ribosomes are examples of molecular machines, and they often take the form of multi-protein complexes. For the last several decades, scientists have attempted, with varying degrees of success, to miniaturize machines found in the macroscopic world. The first example of an artificial molecular machine (AMM) was reported in 1994, featuring a rotaxane with a ring and two different possible binding sites. In 2016 the Nobel Prize in Chemistry was awarded to Jean-Pierre Sauvage, Sir J. Fraser Stoddart, and Bernard L. Feringa for the design and synthesis of molecular machines.

<span class="mw-page-title-main">Molecular motor</span> Biological molecular machines

Molecular motors are natural (biological) or artificial molecular machines that are the essential agents of movement in living organisms. In general terms, a motor is a device that consumes energy in one form and converts it into motion or mechanical work; for example, many protein-based molecular motors harness the chemical free energy released by the hydrolysis of ATP in order to perform mechanical work. In terms of energetic efficiency, this type of motor can be superior to currently available man-made motors. One important difference between molecular motors and macroscopic motors is that molecular motors operate in the thermal bath, an environment in which the fluctuations due to thermal noise are significant.

<span class="mw-page-title-main">Synthetic molecular motor</span> Man-made molecular machines

Synthetic molecular motors are molecular machines capable of continuous directional rotation under an energy input. Although the term "molecular motor" has traditionally referred to a naturally occurring protein that induces motion, some groups also use the term when referring to non-biological, non-peptide synthetic motors. Many chemists are pursuing the synthesis of such molecular motors.

<span class="mw-page-title-main">DNA origami</span> Folding of DNA to create two- and three-dimensional shapes at the nanoscale

DNA origami is the nanoscale folding of DNA to create arbitrary two- and three-dimensional shapes at the nanoscale. The specificity of the interactions between complementary base pairs make DNA a useful construction material, through design of its base sequences. DNA is a well-understood material that is suitable for creating scaffolds that hold other molecules in place or to create structures all on its own.

<span class="mw-page-title-main">Molecular biophysics</span> Interdisciplinary research area

Molecular biophysics is a rapidly evolving interdisciplinary area of research that combines concepts in physics, chemistry, engineering, mathematics and biology. It seeks to understand biomolecular systems and explain biological function in terms of molecular structure, structural organization, and dynamic behaviour at various levels of complexity. This discipline covers topics such as the measurement of molecular forces, molecular associations, allosteric interactions, Brownian motion, and cable theory. Additional areas of study can be found on Outline of Biophysics. The discipline has required development of specialized equipment and procedures capable of imaging and manipulating minute living structures, as well as novel experimental approaches.

AlkB (Alkylation B) is a protein found in E. coli, induced during an adaptive response and involved in the direct reversal of alkylation damage. AlkB specifically removes alkylation damage to single stranded (SS) DNA caused by SN2 type of chemical agents. It efficiently removes methyl groups from 1-methyl adenines, 3-methyl cytosines in SS DNA. AlkB is an alpha-ketoglutarate-dependent hydroxylase, a superfamily non-haem iron-containing proteins. It oxidatively demethylates the DNA substrate. Demethylation by AlkB is accompanied with release of CO2, succinate, and formaldehyde.

John H. Reif is an American academic, and Professor of Computer Science at Duke University, who has made contributions to large number of fields in computer science: ranging from algorithms and computational complexity theory to robotics. He has also published in many other scientific fields including chemistry, optics, and mathematics (in particular graph theory and game theory.

<span class="mw-page-title-main">Artificial enzyme</span>

An artificial enzyme is a synthetic organic molecule or ion that recreates one or more functions of an enzyme. It seeks to deliver catalysis at rates and selectivity observed in naturally occurring enzymes.

<span class="mw-page-title-main">DNA nanotechnology</span> The design and manufacture of artificial nucleic acid structures for technological uses

DNA nanotechnology is the design and manufacture of artificial nucleic acid structures for technological uses. In this field, nucleic acids are used as non-biological engineering materials for nanotechnology rather than as the carriers of genetic information in living cells. Researchers in the field have created static structures such as two- and three-dimensional crystal lattices, nanotubes, polyhedra, and arbitrary shapes, and functional devices such as molecular machines and DNA computers. The field is beginning to be used as a tool to solve basic science problems in structural biology and biophysics, including applications in X-ray crystallography and nuclear magnetic resonance spectroscopy of proteins to determine structures. Potential applications in molecular scale electronics and nanomedicine are also being investigated.

<span class="mw-page-title-main">Spherical nucleic acid</span>

Spherical nucleic acids (SNAs) are nanostructures that consist of a densely packed, highly oriented arrangement of linear nucleic acids in a three-dimensional, spherical geometry. This novel three-dimensional architecture is responsible for many of the SNA's novel chemical, biological, and physical properties that make it useful in biomedicine and materials synthesis. SNAs were first introduced in 1996 by Chad Mirkin’s group at Northwestern University.

Synthetic virology is a branch of virology engaged in the study and engineering of synthetic man-made viruses. It is a multidisciplinary research field at the intersection of virology, synthetic biology, computational biology, and DNA nanotechnology, from which it borrows and integrates its concepts and methodologies. There is a wide range of applications for synthetic viral technology such as medical treatments, investigative tools, and reviving organisms.

Collective motion is defined as the spontaneous emergence of ordered movement in a system consisting of many self-propelled agents. It can be observed in everyday life, for example in flocks of birds, schools of fish, herds of animals and also in crowds and car traffic. It also appears at the microscopic level: in colonies of bacteria, motility assays and artificial self-propelled particles. The scientific community is trying to understand the universality of this phenomenon. In particular it is intensively investigated in statistical physics and in the field of active matter. Experiments on animals, biological and synthesized self-propelled particles, simulations and theories are conducted in parallel to study these phenomena. One of the most famous models that describes such behavior is the Vicsek model introduced by Tamás Vicsek et al. in 1995.

<span class="mw-page-title-main">Toehold mediated strand displacement</span>

Toehold mediated strand displacement (TMSD) is an enzyme-free molecular tool to exchange one strand of DNA or RNA (output) with another strand (input). It is based on the hybridization of two complementary strands of DNA or RNA via Watson-Crick base pairing (A-T/U and C-G) and makes use of a process called branch migration. Although branch migration has been known to the scientific community since the 1970s, TMSD has not been introduced to the field of DNA nanotechnology until 2000 when Yurke et al. was the first who took advantage of TMSD. He used the technique to open and close a set of DNA tweezers made of two DNA helices using an auxiliary strand of DNA as fuel. Since its first use, the technique has been modified for the construction of autonomous molecular motors, catalytic amplifiers, reprogrammable DNA nanostructures and molecular logic gates. It has also been used in conjunction with RNA for the production of kinetically-controlled ribosensors. TMSD starts with a double-stranded DNA complex composed of the original strand and the protector strand. The original strand has an overhanging region the so-called “toehold” which is complementary to a third strand of DNA referred to as the “invading strand”. The invading strand is a sequence of single-stranded DNA (ssDNA) which is complementary to the original strand. The toehold regions initiate the process of TMSD by allowing the complementary invading strand to hybridize with the original strand, creating a DNA complex composed of three strands of DNA. This initial endothermic step is rate limiting and can be tuned by varying the strength (length and sequence composition e.g. G-C or A-T rich strands) of the toehold region. The ability to tune the rate of strand displacement over a range of 6 orders of magnitude generates the backbone of this technique and allows the kinetic control of DNA or RNA devices. After the binding of the invading strand and the original strand occurred, branch migration of the invading domain then allows the displacement of the initial hybridized strand (protector strand). The protector strand can possess its own unique toehold and can, therefore, turn into an invading strand itself, starting a strand-displacement cascade. The whole process is energetically favored and although a reverse reaction can occur its rate is up to 6 orders of magnitude slower. Additional control over the system of toehold mediated strand displacement can be introduced by toehold sequestering.

TectoRNAs are modular RNA units able to self-assemble into larger nanostructures in a programmable fashion. They are generated by rational design through an approach called RNA architectonics, which make use of RNA structural modules identified in natural RNA molecules to form pre-defined 3D structures spontaneously.

References

  1. Reif JH (2003). "The Design of Autonomous DNA Nanomechanical Devices: Walking and Rolling DNA". Natural Computing. 2 (15): 439–461. CiteSeerX   10.1.1.4.291 . doi:10.1023/B:NACO.0000006775.03534.92. S2CID   6200417.
  2. Shin JS, Pierce NA (September 2004). "A synthetic DNA walker for molecular transport". Journal of the American Chemical Society. 126 (35): 10834–10835. doi:10.1021/ja047543j. PMID   15339155.
  3. Yin P, Yan H, Daniell XG, Turberfield AJ, Reif JH (September 2004). "A unidirectional DNA walker that moves autonomously along a track". Angewandte Chemie. 43 (37): 4906–4911. doi:10.1002/anie.200460522. PMID   15372637.
  4. Thubagere AJ, Li W, Johnson RF, Chen Z, Doroudi S, Lee YL, et al. (September 2017). "A cargo-sorting DNA robot". Science. 357 (6356): eaan6558. doi: 10.1126/science.aan6558 . PMID   28912216.
  5. 1 2 3 Simmel FC (October 2009). "Processive motion of bipedal DNA walkers". ChemPhysChem. 10 (15): 2593–2597. doi:10.1002/cphc.200900493. PMID   19739195.
  6. 1 2 Pan J, Li F, Cha TG, Chen H, Choi JH (August 2015). "Recent progress on DNA based walkers". Current Opinion in Biotechnology. 34: 56–64. doi:10.1016/j.copbio.2014.11.017. PMID   25498478.
  7. 1 2 Leigh D (April 2014). "Synthetic DNA Walkers". Top Curr Chem. Topics in Current Chemistry. 354: 111–38. doi:10.1007/128_2014_546. ISBN   978-3-319-08677-4. PMID   24770565.
  8. You M, Chen Y, Zhang X, Liu H, Wang R, Wang K, et al. (March 2012). "An autonomous and controllable light-driven DNA walking device". Angewandte Chemie. 51 (10): 2457–2460. doi:10.1002/anie.201107733. PMC   3843772 . PMID   22298502.
  9. Škugor M, Valero J, Murayama K, Centola M, Asanuma H, Famulok M (May 2019). "Orthogonally Photocontrolled Non-Autonomous DNA Walker". Angewandte Chemie. 58 (21): 6948–6951. doi:10.1002/anie.201901272. PMID   30897257. S2CID   85446523.
  10. Bath J (July 11, 2005). "A free-running DNA motor powered by a nicking enzyme". Angewandte Chemie International Edition. 117 (28): 4432–4435. Bibcode:2005AngCh.117.4432B. doi:10.1002/ange.200501262.
  11. Lund K, Manzo AJ, Dabby N, Michelotti N, Johnson-Buck A, Nangreave J, et al. (May 2010). "Molecular robots guided by prescriptive landscapes". Nature. 465 (7295): 206–210. Bibcode:2010Natur.465..206L. doi:10.1038/nature09012. PMC   2907518 . PMID   20463735.
  12. Gu H, Chao J, Xiao SJ, Seeman NC (May 2010). "A proximity-based programmable DNA nanoscale assembly line". Nature. 465 (7295): 202–205. Bibcode:2010Natur.465..202G. doi:10.1038/nature09026. PMC   2872101 . PMID   20463734.
  13. He Y, Liu DR (November 2010). "Autonomous multistep organic synthesis in a single isothermal solution mediated by a DNA walker". Nature Nanotechnology. 5 (11): 778–782. Bibcode:2010NatNa...5..778H. doi:10.1038/nnano.2010.190. PMC   2974042 . PMID   20935654.
  14. Yehl K, Mugler A, Vivek S, Liu Y, Zhang Y, Fan M, et al. (February 2016). "High-speed DNA-based rolling motors powered by RNase H". Nature Nanotechnology. 11 (2): 184–190. Bibcode:2016NatNa..11..184Y. doi:10.1038/nnano.2015.259. PMC   4890967 . PMID   26619152.
  15. Valero J, Pal N, Dhakal S, Walter NG, Famulok M (June 2018). "A bio-hybrid DNA rotor-stator nanoengine that moves along predefined tracks". Nature Nanotechnology. 13 (6): 496–503. Bibcode:2018NatNa..13..496V. doi:10.1038/s41565-018-0109-z. PMC   5994166 . PMID   29632399.
  16. Boehm F (Nov 18, 2013). Nanomedical Device and Systems Design: Challenges, Possibilities, Visions. CRC Press. ISBN   9781439863237.
  17. 1 2 "Nano-walkers take speedy leap forward with first rolling DNA-based motor". phys.org. Retrieved 2015-12-04.
  18. "Chapter 18 : DNA Nano Robotics – NanoTechnology Journal & Publications". NanoTechnology Journal & Publications. Archived from the original on 2015-12-08. Retrieved 2015-12-04.
  19. "Gymnastic feats help DNA 'walker' set speed record". Nature. 557 (7705): 283. May 2018. doi: 10.1038/d41586-018-05127-8 . PMID   29760489.