International Journal of Molecular Sciences

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28 pages, 3851 KiB

Open AccessArticle

Oritatami: A Computational Model for Molecular Co-Transcriptional Folding

by Cody Geary, Pierre-Étienne Meunier, Nicolas Schabanel and Shinnosuke Seki

Int. J. Mol. Sci. 2019, 20(9), 2259; https://doi.org/10.3390/ijms20092259 - 7 May 2019

Cited by 14 | Viewed by 3612

Abstract

We introduce and study the computational power of Oritatami, a theoretical model that explores greedy molecular folding, whereby a molecular strand begins to fold before its production is complete. This model is inspired by our recent experimental work demonstrating the construction of shapes [...] Read more.

We introduce and study the computational power of Oritatami, a theoretical model that explores greedy molecular folding, whereby a molecular strand begins to fold before its production is complete. This model is inspired by our recent experimental work demonstrating the construction of shapes at the nanoscale from RNA, where strands of RNA fold into programmable shapes during their transcription from an engineered sequence of synthetic DNA. In the model of Oritatami, we explore the process of folding a single-strand bit by bit in such a way that the final fold emerges as a space-time diagram of computation. One major requirement in order to compute within this model is the ability to program a single sequence to fold into different shapes dependent on the state of the surrounding inputs. Another challenge is to embed all of the computing components within a contiguous strand, and in such a way that different fold patterns of the same strand perform different functions of computation. Here, we introduce general design techniques to solve these challenges in the Oritatami model. Our main result in this direction is the demonstration of a periodic Oritatami system that folds upon itself algorithmically into a prescribed set of shapes, depending on its current local environment, and whose final folding displays the sequence of binary integers from 0 to

N = 2^{k} - 1

with a seed of size

O (k)

. We prove that designing Oritatami is NP-hard in the number of possible local environments for the folding. Nevertheless, we provide an efficient algorithm, linear in the length of the sequence, that solves the Oritatami design problem when the number of local environments is a small fixed constant. This shows that this problem is in fact fixed parameter tractable (FPT) and can thus be solved in practice efficiently. We hope that the numerous structural strategies employed in Oritatami enabling computation will inspire new architectures for computing in RNA that take advantage of the rapid kinetic-folding of RNA. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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19 pages, 4103 KiB

Open AccessArticle

Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence

by Christin Möser, Jessica S. Lorenz, Martin Sajfutdinow and David M. Smith

Int. J. Mol. Sci. 2018, 19(11), 3482; https://doi.org/10.3390/ijms19113482 - 6 Nov 2018

Cited by 15 | Viewed by 5616

Abstract

DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized [...] Read more.

DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2’s natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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18 pages, 8782 KiB

Open AccessArticle

Review of the Electrical Characterization of Metallic Nanowires on DNA Templates

by Türkan Bayrak, Nagesh S. Jagtap and Artur Erbe

Int. J. Mol. Sci. 2018, 19(10), 3019; https://doi.org/10.3390/ijms19103019 - 3 Oct 2018

Cited by 15 | Viewed by 4941

Abstract

The use of self-assembly techniques may open new possibilities in scaling down electronic circuits to their ultimate limits. Deoxyribonucleic acid (DNA) nanotechnology has already demonstrated that it can provide valuable tools for the creation of nanostructures of arbitrary shape, therefore presenting an ideal [...] Read more.

The use of self-assembly techniques may open new possibilities in scaling down electronic circuits to their ultimate limits. Deoxyribonucleic acid (DNA) nanotechnology has already demonstrated that it can provide valuable tools for the creation of nanostructures of arbitrary shape, therefore presenting an ideal platform for the development of nanoelectronic circuits. So far, however, the electronic properties of DNA nanostructures are mostly insulating, thus limiting the use of the nanostructures in electronic circuits. Therefore, methods have been investigated that use the DNA nanostructures as templates for the deposition of electrically conducting materials along the DNA strands. The most simple such structure is given by metallic nanowires formed by deposition of metals along the DNA nanostructures. Here, we review the fabrication and the characterization of the electronic properties of nanowires, which were created using these methods. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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11 pages, 4338 KiB

Open AccessArticle

Noise Analysis of Monolayer Graphene Nanopores

by Zi-Yin Zhang, Yun-Sheng Deng, Hai-Bing Tian, Han Yan, Hong-Liang Cui and De-Qiang Wang

Int. J. Mol. Sci. 2018, 19(9), 2639; https://doi.org/10.3390/ijms19092639 - 6 Sep 2018

Cited by 20 | Viewed by 4583

Abstract

Graphene-based nanopore devices have shown tantalizing potential in single molecule detection for their monoatomic membrane thickness which is roughly equal to the gap between nucleobases. However, high noise level hampers applications of graphene nanopore sensors, especially at low frequencies. In this article, we [...] Read more.

Graphene-based nanopore devices have shown tantalizing potential in single molecule detection for their monoatomic membrane thickness which is roughly equal to the gap between nucleobases. However, high noise level hampers applications of graphene nanopore sensors, especially at low frequencies. In this article, we report on a study of the contribution of suspended graphene area to noise level in full frequency band. Monolayer graphene films are transferred onto SiN_x substrates preset with holes in varied diameters and formed self-supported films. After that, the films are perforated with smaller, nanoscale holes. Experimental studies indicate a dependency of low-frequency 1/f noise on the underlying SiN_x geometry. The contribution of the suspended graphene area to capacitance which affects the noise level in the high frequency range reveals that the graphene free-standing film area influences noise level over a wide frequency region. In addition, the low-frequency noise demonstrates a weak dependency on salt concentration, in deviation from Hooge’s relation. These findings and attendant analysis provide a systematic understanding of the noise characteristics and can serve as a guide to designing free-standing monolayer graphene nanopore devices. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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19 pages, 4007 KiB

Open AccessArticle

Towards a Bioelectronic Computer: A Theoretical Study of a Multi-Layer Biomolecular Computing System That Can Process Electronic Inputs

by Katherine E. Dunn, Martin A. Trefzer, Steven Johnson and Andy M. Tyrrell

Int. J. Mol. Sci. 2018, 19(9), 2620; https://doi.org/10.3390/ijms19092620 - 4 Sep 2018

Cited by 4 | Viewed by 3997

Abstract

DNA molecular machines have great potential for use in computing systems. Since Adleman originally introduced the concept of DNA computing through his use of DNA strands to solve a Hamiltonian path problem, a range of DNA-based computing elements have been developed, including logic [...] Read more.

DNA molecular machines have great potential for use in computing systems. Since Adleman originally introduced the concept of DNA computing through his use of DNA strands to solve a Hamiltonian path problem, a range of DNA-based computing elements have been developed, including logic gates, neural networks, finite state machines (FSMs) and non-deterministic universal Turing machines. DNA molecular machines can be controlled using electrical signals and the state of DNA nanodevices can be measured using electrochemical means. However, to the best of our knowledge there has as yet been no demonstration of a fully integrated biomolecular computing system that has multiple levels of information processing capacity, can accept electronic inputs and is capable of independent operation. Here we address the question of how such a system could work. We present simulation results showing that such an integrated hybrid system could convert electrical impulses into biomolecular signals, perform logical operations and take a decision, storing its history. We also illustrate theoretically how the system might be able to control an autonomous robot navigating through a maze. Our results suggest that a system of the proposed type is technically possible but for practical applications significant advances would be required to increase its speed. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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11 pages, 4956 KiB

Open AccessArticle

Boron-Implanted Silicon Substrates for Physical Adsorption of DNA Origami

by Sadao Takabayashi, Shohei Kotani, Juan Flores-Estrada, Elijah Spears, Jennifer E. Padilla, Lizandra C. Godwin, Elton Graugnard, Wan Kuang, Scott Sills and William L. Hughes

Int. J. Mol. Sci. 2018, 19(9), 2513; https://doi.org/10.3390/ijms19092513 - 24 Aug 2018

Cited by 8 | Viewed by 5089

Abstract

DNA nanostructures routinely self-assemble with sub-10 nm feature sizes. This capability has created industry interest in using DNA as a lithographic mask, yet with few exceptions, solution-based deposition of DNA nanostructures has remained primarily academic to date. En route to controlled adsorption of [...] Read more.

DNA nanostructures routinely self-assemble with sub-10 nm feature sizes. This capability has created industry interest in using DNA as a lithographic mask, yet with few exceptions, solution-based deposition of DNA nanostructures has remained primarily academic to date. En route to controlled adsorption of DNA patterns onto manufactured substrates, deposition and placement of DNA origami has been demonstrated on chemically functionalized silicon substrates. While compelling, chemical functionalization adds fabrication complexity that limits mask efficiency and hence industry adoption. As an alternative, we developed an ion implantation process that tailors the surface potential of silicon substrates to facilitate adsorption of DNA nanostructures without the need for chemical functionalization. Industry standard 300 mm silicon wafers were processed, and we showed controlled adsorption of DNA origami onto boron-implanted silicon patterns; selective to a surrounding silicon oxide matrix. The hydrophilic substrate achieves very high surface selectivity by exploiting pH-dependent protonation of silanol-groups on silicon dioxide (SiO₂), across a range of solution pH values and magnesium chloride (MgCl₂) buffer concentrations. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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12 pages, 5858 KiB

Open AccessArticle

Fabrication and Characterization of Finite-Size DNA 2D Ring and 3D Buckyball Structures

by Soojin Jo, Seungjae Kim, Byung Ho Lee, Anshula Tandon, Byunghoon Kim, Sung Ha Park and Moon Ki Kim

Int. J. Mol. Sci. 2018, 19(7), 1895; https://doi.org/10.3390/ijms19071895 - 27 Jun 2018

Cited by 7 | Viewed by 4361

Abstract

In order to incorporate functionalization into synthesized DNA nanostructures, enhance their production yield, and utilize them in various applications, it is necessary to study their physical stabilities and dynamic characteristics. Although simulation-based analysis used for DNA nanostructures provides important clues to explain their [...] Read more.

In order to incorporate functionalization into synthesized DNA nanostructures, enhance their production yield, and utilize them in various applications, it is necessary to study their physical stabilities and dynamic characteristics. Although simulation-based analysis used for DNA nanostructures provides important clues to explain their self-assembly mechanism, structural function, and intrinsic dynamic characteristics, few studies have focused on the simulation of DNA supramolecular structures due to the structural complexity and high computational cost. Here, we demonstrated the feasibility of using normal mode analysis for relatively complex DNA structures with larger molecular weights, i.e., finite-size DNA 2D rings and 3D buckyball structures. The normal mode analysis was carried out using the mass-weighted chemical elastic network model (MWCENM) and the symmetry-constrained elastic network model (SCENM), both of which are precise and efficient modeling methodologies. MWCENM considers both the weight of the nucleotides and the chemical bonds between atoms, and SCENM can obtain mode shapes of a whole structure by using only a repeated unit and its connectivity with neighboring units. Our results show the intrinsic vibrational features of DNA ring structures, which experience inner/outer circle and bridge motions, as well as DNA buckyball structures having overall breathing and local breathing motions. These could be used as the fundamental basis for designing and constructing more complicated DNA nanostructures. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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10 pages, 1515 KiB

Open AccessCommunication

Tuning the Mechanical Properties of a DNA Hydrogel in Three Phases Based on ATP Aptamer

by Hengyuan Liu, Tianyang Cao, Yun Xu, Yuanchen Dong and Dongsheng Liu

Int. J. Mol. Sci. 2018, 19(6), 1633; https://doi.org/10.3390/ijms19061633 - 31 May 2018

Cited by 36 | Viewed by 8377

Abstract

By integrating ATP aptamer into the linker DNA, a novel DNA hydrogel was designed, with mechanical properties that could be tuned into three phases. Based on the unique interaction between ATP and its aptamer, the mechanical strength of the hydrogel increased from 204 [...] Read more.

By integrating ATP aptamer into the linker DNA, a novel DNA hydrogel was designed, with mechanical properties that could be tuned into three phases. Based on the unique interaction between ATP and its aptamer, the mechanical strength of the hydrogel increased from 204 Pa to 380 Pa after adding ATP. Furthermore, with the addition of the complementary sequence to the ATP aptamer, the mechanical strength could be increased to 570 Pa. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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19 pages, 4469 KiB

Open AccessArticle

Skeleton-Controlled pDNA Delivery of Renewable Steroid-Based Cationic Lipids, the Endocytosis Pathway Analysis and Intracellular Localization

by Ruilong Sheng, Zhao Wang, Ting Luo, Amin Cao, Jingjing Sun and Joseph M. Kinsella

Int. J. Mol. Sci. 2018, 19(2), 369; https://doi.org/10.3390/ijms19020369 - 26 Jan 2018

Cited by 6 | Viewed by 4170

Abstract

Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient [...] Read more.

Using renewable and biocompatible natural-based resources to construct functional biomaterials has attracted great attention in recent years. In this work, we successfully prepared a series of steroid-based cationic lipids by integrating various steroid skeletons/hydrophobes with (l-)-arginine headgroups via facile and efficient synthetic approach. The plasmid DNA (pDNA) binding affinity of the steroid-based cationic lipids, average particle sizes, surface potentials, morphologies and stability of the steroid-based cationic lipids/pDNA lipoplexes were disclosed to depend largely on the steroid skeletons. Cellular evaluation results revealed that cytotoxicity and gene transfection efficiency of the steroid-based cationic lipids in H1299 and HeLa cells strongly relied on the steroid hydrophobes. Interestingly, the steroid lipids/pDNA lipoplexes inclined to enter H1299 cells mainly through caveolae and lipid-raft mediated endocytosis pathways, and an intracellular trafficking route of “lipid-raft-mediated endocytosis→lysosome→cell nucleic localization” was accordingly proposed. The study provided possible approach for developing high-performance steroid-based lipid gene carriers, in which the cytotoxicity, gene transfection capability, endocytosis pathways, and intracellular trafficking/localization manners could be tuned/controlled by introducing proper steroid skeletons/hydrophobes. Noteworthy, among the lipids, Cho-Arg showed remarkably high gene transfection efficacy, even under high serum concentration (50% fetal bovine serum), making it an efficient gene transfection agent for practical application. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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Review

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13 pages, 971 KiB

Open AccessReview

Cancer Vaccine Immunotherapy with RNA-Loaded Liposomes

by Elias J. Sayour, Hector R. Mendez-Gomez and Duane A. Mitchell

Int. J. Mol. Sci. 2018, 19(10), 2890; https://doi.org/10.3390/ijms19102890 - 23 Sep 2018

Cited by 47 | Viewed by 7252

Abstract

Cancer vaccines may be harnessed to incite immunity against poorly immunogenic tumors, however they have failed in therapeutic settings. Poor antigenicity coupled with systemic and intratumoral immune suppression have been significant drawbacks. RNA encoding for tumor associated or specific epitopes can serve as [...] Read more.

Cancer vaccines may be harnessed to incite immunity against poorly immunogenic tumors, however they have failed in therapeutic settings. Poor antigenicity coupled with systemic and intratumoral immune suppression have been significant drawbacks. RNA encoding for tumor associated or specific epitopes can serve as a more immunogenic and expeditious trigger of anti-tumor immunity. RNA stimulates innate immunity through toll like receptor stimulation producing type I interferon, and it mediates potent adaptive responses. Since RNA is inherently unstable, delivery systems have been developed to protect and deliver it to intended targets in vivo. In this review, we discuss liposomes as RNA delivery vehicles and their role as cancer vaccines. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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18 pages, 3444 KiB

Open AccessReview

Amphiphilic DNA Organic Hybrids: Functional Materials in Nanoscience and Potential Application in Biomedicine

by Zhiyong Zhao, Ting Du, Feng Liang and Simin Liu

Int. J. Mol. Sci. 2018, 19(8), 2283; https://doi.org/10.3390/ijms19082283 - 3 Aug 2018

Cited by 18 | Viewed by 5867

Abstract

Due to the addressability and programmability, DNA has been applied not merely in constructing static elegant nanostructures such as two dimensional and three dimensional DNA nanostructures but also in designing dynamic nanodevices. Moreover, DNA could combine with hydrophobic organic molecules to be a [...] Read more.

Due to the addressability and programmability, DNA has been applied not merely in constructing static elegant nanostructures such as two dimensional and three dimensional DNA nanostructures but also in designing dynamic nanodevices. Moreover, DNA could combine with hydrophobic organic molecules to be a new amphiphilic building block and then self-assemble into nanomaterials. Of particular note, a recent state-of-the-art research has turned our attention to the amphiphilic DNA organic hybrids including small molecule modified DNA (lipid-DNA, fluorescent molecule-DNA, etc.), DNA block copolymers, and DNA-dendron hybrids. This review focuses mainly on the development of their self-assembly behavior and their potential application in nanomaterial and biomedicine. The potential challenges regarding of the amphiphilic DNA organic hybrids are also briefly discussed, aiming to advance their practical applications in nanoscience and biomedicine. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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17 pages, 1617 KiB

Open AccessReview

Dynamic DNA Origami Devices: from Strand-Displacement Reactions to External-Stimuli Responsive Systems

by Heini Ijäs, Sami Nummelin, Boxuan Shen, Mauri A. Kostiainen and Veikko Linko

Int. J. Mol. Sci. 2018, 19(7), 2114; https://doi.org/10.3390/ijms19072114 - 20 Jul 2018

Cited by 69 | Viewed by 10265

Abstract

DNA nanotechnology provides an excellent foundation for diverse nanoscale structures that can be used in various bioapplications and materials research. Among all existing DNA assembly techniques, DNA origami proves to be the most robust one for creating custom nanoshapes. Since its invention in [...] Read more.

DNA nanotechnology provides an excellent foundation for diverse nanoscale structures that can be used in various bioapplications and materials research. Among all existing DNA assembly techniques, DNA origami proves to be the most robust one for creating custom nanoshapes. Since its invention in 2006, building from the bottom up using DNA advanced drastically, and therefore, more and more complex DNA-based systems became accessible. So far, the vast majority of the demonstrated DNA origami frameworks are static by nature; however, there also exist dynamic DNA origami devices that are increasingly coming into view. In this review, we discuss DNA origami nanostructures that exhibit controlled translational or rotational movement when triggered by predefined DNA sequences, various molecular interactions, and/or external stimuli such as light, pH, temperature, and electromagnetic fields. The rapid evolution of such dynamic DNA origami tools will undoubtedly have a significant impact on molecular-scale precision measurements, targeted drug delivery and diagnostics; however, they can also play a role in the development of optical/plasmonic sensors, nanophotonic devices, and nanorobotics for numerous different tasks. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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16 pages, 58979 KiB

Open AccessReview

DNA Nanotechnology for Cancer Diagnosis and Therapy

by Tianshu Chen, Lingjie Ren, Xiaohao Liu, Mengru Zhou, Lingling Li, Jingjing Xu and Xiaoli Zhu

Int. J. Mol. Sci. 2018, 19(6), 1671; https://doi.org/10.3390/ijms19061671 - 5 Jun 2018

Cited by 84 | Viewed by 14990

Abstract

Cancer is one of the leading causes of mortality worldwide, because of the lack of accurate diagnostic tools for the early stages of cancer. Thus, early diagnosis, which provides important information for a timely therapy of cancer, is of great significance for controlling [...] Read more.

Cancer is one of the leading causes of mortality worldwide, because of the lack of accurate diagnostic tools for the early stages of cancer. Thus, early diagnosis, which provides important information for a timely therapy of cancer, is of great significance for controlling the development of the disease and the proliferation of cancer cells and for improving the survival rates of patients. To achieve the goals of early diagnosis and timely therapy of cancer, DNA nanotechnology may be effective, since it has emerged as a valid technique for the fabrication of various nanoscale structures and devices. The resultant DNA-based nanoscale structures and devices show extraordinary performance in cancer diagnosis, owing to their predictable secondary structures, small sizes, and high biocompatibility and programmability. In particular, the rapid development of DNA nanotechnologies, such as molecular assembly technologies, endows DNA-based nanomaterials with more functionalization and intellectualization. Here, we summarize recent progress made in the development of DNA nanotechnology for the fabrication of functional and intelligent nanomaterials and highlight the prospects of this technology in cancer diagnosis and therapy. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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13 pages, 1043 KiB

Open AccessReview

Nanomotors for Nucleic Acid, Proteins, Pollutants and Cells Detection

by Alejandro Baeza and María Vallet-Regí

Int. J. Mol. Sci. 2018, 19(6), 1579; https://doi.org/10.3390/ijms19061579 - 25 May 2018

Cited by 14 | Viewed by 4376

Abstract

The development of nanomachines able to operate at the nanoscale, performing complex tasks such as drug delivery, precision surgery, or cell detection, constitutes one of the most important challenges in nanotechnology. The principles that rule the nanoscale are completely different from the ones [...] Read more.

The development of nanomachines able to operate at the nanoscale, performing complex tasks such as drug delivery, precision surgery, or cell detection, constitutes one of the most important challenges in nanotechnology. The principles that rule the nanoscale are completely different from the ones which govern the macroscopic world and, therefore, the collaboration of scientists with expertise in different fields is required for the effective fabrication of these tiny machines. In this review, the most recent advances carried out in the synthesis and application of nanomachines for diagnosis applications will be presented in order to provide a picture of their potential in the detection of important biomolecules or pathogens in a selective and controlled manner. Full article

(This article belongs to the Special Issue Nucleic Acid Nanotechnology)

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