DNA nanotechnology-empowered nanoscopic imaging of biomolecules

2021 ◽  
Author(s):  
Fan Li ◽  
Jiang Li ◽  
Baijun Dong ◽  
Fei Wang ◽  
Chunhai Fan ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Nanostructures ◽  
Dna Nanostructure ◽  
Imaging Probes

DNA nanotechnology has led to the rise of DNA nanostructures, which possess programmable shapes and are capable of organizing different functional molecules and materials. A variety of DNA nanostructure-based imaging probes have been developed.

scholarly journals Determinants of ligand-functionalized DNA nanostructure-cell interactions

2021 ◽  
Author(s):  
Glenn A.O. Cremers ◽  
Bas J.H.M. Rosier ◽  
Ab Meijs ◽  
Nicholas B. Tito ◽  
Sander M.J. van Duijnhoven ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dna Nanotechnology ◽  
Absolute Number ◽  
Design Parameters ◽  
Dna Nanostructures ◽  
Surface Receptors ◽  
Protein Ligands ◽  
Dna Nanostructure ◽  
Functionalized Nanomaterials ◽  
Ligand Orientation

AbstractSynthesis of ligand-functionalized nanomaterials with control over size, shape and ligand orientation, facilitates the design of tailored nanomedicines for therapeutic purposes. DNA nanotechnology has emerged as a powerful tool to rationally construct two- and three-dimensional nanostructures, enabling site-specific incorporation of protein ligands with control over stoichiometry and orientation. To efficiently target cell surface receptors, exploration of the parameters that modulate cellular accessibility of these nanostructures is essential. In this study we systematically investigate tunable design parameters of antibody-functionalized DNA nanostructures binding to therapeutically relevant receptors. We show that, although the native affinity of antibody-functionalized DNA nanostructures remains unaltered, the absolute number of bound surface receptors is lower compared to soluble antibodies and is mainly governed by nanostructure size and DNA handle location. The obtained results provide key insights in the ability of ligand-functionalized DNA nanostructures to bind surface receptors and yields design rules for optimal cellular targeting.

scholarly journals Adenita: interactive 3D modelling and visualization of DNA nanostructures

2020 ◽  
Vol 48 (15) ◽  
pp. 8269-8275 ◽  
Author(s):  
Elisa de Llano ◽  
Haichao Miao ◽  
Yasaman Ahmadi ◽  
Amanda J Wilson ◽  
Morgan Beeby ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Software Tool ◽  
Building Blocks ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
User Interactions ◽  
Dna Nanostructure ◽  
Dna Tiles ◽  
The Creation ◽  
Interactive 3D

Abstract DNA nanotechnology is a rapidly advancing field, which increasingly attracts interest in many different disciplines, such as medicine, biotechnology, physics and biocomputing. The increasing complexity of novel applications requires significant computational support for the design, modelling and analysis of DNA nanostructures. However, current in silico design tools have not been developed in view of these new applications and their requirements. Here, we present Adenita, a novel software tool for the modelling of DNA nanostructures in a user-friendly environment. A data model supporting different DNA nanostructure concepts (multilayer DNA origami, wireframe DNA origami, DNA tiles etc.) has been developed allowing the creation of new and the import of existing DNA nanostructures. In addition, the nanostructures can be modified and analysed on-the-fly using an intuitive toolset. The possibility to combine and re-use existing nanostructures as building blocks for the creation of new superstructures, the integration of alternative molecules (e.g. proteins, aptamers) during the design process, and the export option for oxDNA simulations are outstanding features of Adenita, which spearheads a new generation of DNA nanostructure modelling software. We showcase Adenita by re-using a large nanorod to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.

scholarly journals Choice of fluorophore affects dynamic DNA nanostructures

2020 ◽  
Author(s):  
Kevin Jahnke ◽  
Helmut Grubmüller ◽  
Maxim Igaev ◽  
Kerstin Göpfrich
Keyword(s):  
Energy Landscape ◽  
Dna Nanotechnology ◽  
Reaction Diffusion ◽  
Md Simulations ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Diffusion Modeling ◽  
Ph Responsive ◽  
Dna Nanostructure ◽  
Potential Impact

The ability to dynamically remodel DNA origami structures or functional nanodevices is highly desired in the field of DNA nanotechnology. Concomitantly, the use of fluorophores to track and validate the dynamics of such DNA-based architectures is commonplace and often unavoidable. It is therefore crucial to be aware of the side effects of popular fluorophores, which are often exchanged without considering the potential impact on the system. Here, we show that the choice of fluorophore can strongly affect the reconfiguration of DNA nanostructures. To this end, we encapsulate a triple-stranded DNA (tsDNA) into water-in-oil compartments and functionalize their periphery with a single-stranded DNA handle (ssDNA). Thus, the tsDNA can bind and unbind from the periphery by reversible opening of the triplex and subsequent strand displacement. Using a combination of experiments, molecular dynamics (MD) simulations, and reaction-diffusion modeling, we demonstrate for twelve different fluorophore combinations that it is possible to alter or even inhibit the DNA nanostructure formation - without changing the DNA sequence. Besides its immediate importance for the design of pH-responsive switches and fluorophore labelling, our work presents a strategy to precisely tune the energy landscape of dynamic DNA nanodevices.

scholarly journals Ultrasound exposure enhances cellular uptake of nanoscale cargos

2021 ◽  
Author(s):  
Kahkashan Bansal ◽  
Anjali Rajwar ◽  
Himanshu Shekhar ◽  
Dhiraj Bhatia
Keyword(s):  
Drug Delivery ◽  
Cellular Uptake ◽  
Propidium Iodide ◽  
Dna Nanotechnology ◽  
Chemotherapeutic Agents ◽  
Dna Nanostructures ◽  
Ultrasound Exposure ◽  
Dna Nanostructure ◽  
Cellular Components ◽  
Further Development

DNA nanotechnology utilizes DNA as a structural molecule to design palette of nanostructures with different shapes and sizes. DNA nanocages have demonstrated significant potential for drug delivery. Therefore, enhancing the delivery of DNA nanocages into cells can improve their efficacy as drug delivery agents. Numerous studies have reported the effects of ultrasound for enhancing drug delivery across biological barriers. The mechanical bioeffects caused by cell-ultrasound interaction can cause sonoporation, leading to enhanced uptake of drugs, nanoparticles, and chemotherapeutic agents through membranes. Whether ultrasound exposure can enhance the delivery of DNA nanocages has not been explored, which is the focus of this study. Specifically, we investigated the effects of ultrasound on the cellular uptake of propidium Iodide, fluorescent dextrans, and DNA nanostructures). We provide evidence of modulation of pore formation in the cell membrane by ultrasound by studying the intracellular uptake of the impermeable dye, propidium iodide. Treatment of cells with low amplitudes of ultrasound enhanced the uptake of different sizes of dextrans and DNA based nanodevices. These findings could serve as the foundation for further development ultrasound-enabled DNA nanostructure delivery and for specific understanding of underlying biological mechanisms of interaction between ultrasound parameters and cellular components; the knowledge that can be further explored for potential biological and biomedical applications.

scholarly journals In vivo cloning of artificial DNA nanostructures

2008 ◽  
Vol 105 (46) ◽  
pp. 17626-17631 ◽  
Author(s):  
Chenxiang Lin ◽  
Sherri Rinker ◽  
Xing Wang ◽  
Yan Liu ◽  
Nadrian C. Seeman ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Nanostructures ◽  
Scientific Enterprise ◽  
Dna Nanostructure ◽  
Copy Numbers ◽  
Artificial Dna ◽  
Difficult Challenge ◽  
Endonuclease Vii

Mimicking nature is both a key goal and a difficult challenge for the scientific enterprise. DNA, well known as the genetic-information carrier in nature, can be replicated efficiently in living cells. Today, despite the dramatic evolution of DNA nanotechnology, a versatile method that replicates artificial DNA nanostructures with complex secondary structures remains an appealing target. Previous success in replicating DNA nanostructures enzymatically in vitro suggests that a possible solution could be cloning these nanostructures by using viruses. Here, we report a system where a single-stranded DNA nanostructure (Holliday junction or paranemic cross-over DNA) is inserted into a phagemid, transformed into XL1-Blue cells and amplified in vivo in the presence of helper phages. High copy numbers of cloned nanostructures can be obtained readily by using standard molecular biology techniques. Correct replication is verified by a number of assays including nondenaturing PAGE, Ferguson analysis, endonuclease VII digestion, and hydroxyl radical autofootprinting. The simplicity, efficiency, and fidelity of nature are fully reflected in this system. UV-induced psoralen cross-linking is used to probe the secondary structure of the inserted junction in infected cells. Our data suggest the possible formation of the immobile four-arm junction in vivo.

scholarly journals Membrane activity of a DNA-based ion channel depends on the stability of its double-stranded structure.

2021 ◽  
Author(s):  
Diana Morzy ◽  
Himanshu Joshi ◽  
Sarah E Sandler ◽  
Aleksei Aksimentiev ◽  
Ulrich F Keyser
Keyword(s):  
Ion Channels ◽  
Lipid Bilayer ◽  
Lipid Membranes ◽  
Degrees Of Freedom ◽  
Dna Nanotechnology ◽  
Md Simulations ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Dna Nanostructure ◽  
Synthetic Ion Channels

Structural DNA nanotechnology has emerged as a promising method for designing spontaneously-inserting and fully-controllable synthetic ion channels. However, both insertion efficiency and stability of existing DNA-based ion channels leave much room for improvement. Here, we demonstrate an approach to overcoming the unfavorable DNA-lipid interactions that hinder the formation of a stable transmembrane pore. Our all-atom MD simulations and experiments show that the insertion-driving cholesterol modifications, when introduced at an end of a DNA strand, are likely to cause fraying of the terminal base pairs as the DNA nanostructure adopts its energy-minimum configuration in the membrane. We also find that fraying of base pairs distorts nicked DNA constructs when embedded in a lipid bilayer. Here, we show that DNA nanostructures that do not have discontinuities (nicks) in their DNA backbones form considerably more stable DNA-induced conductive pores and insert into lipid membranes with a higher efficiency than the equivalent nicked constructs. Moreover, lack of nicks allows to design and maintain membrane-spanning helices in a tilted orientation within lipid bilayer. Thus, reducing the conformational degrees of freedom of the DNA nanostructures enables better control over their function as synthetic ion channels.

Advances in DNA Nanostructure-Based Smart Drug Delivery Systems

Nano LIFE ◽  
2017 ◽  
Vol 07 (01) ◽  
pp. 1730001 ◽  
Author(s):  
Xingjie Hu ◽  
Zejun Wang ◽  
Chunhai Fan ◽  
Haiyun Song
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Water Solubility ◽  
Dna Nanotechnology ◽  
Delivery Systems ◽  
Structure Design ◽  
Dna Nanostructures ◽  
Cellular Delivery ◽  
Nanoscale Systems ◽  
Dna Nanostructure

Highly specific deoxyribonucleic acid (DNA) base-pairing not only carries genetic information, but also provides the basis for self-assembly of novel nanostructures with programmable shapes and sizes. Unlike single-stranded and double-stranded DNA, DNA nanostructures exhibit good cellular permeability. They also have characteristics of uniform size, easy functionalization, precise addressability, excellent water solubility and high biocompatibility. Due to their unique properties, these tailored molecular devices are ideal nanoscale systems for targeting cells and triggering cellular responses. Recent progress in the field of DNA nanotechnology has demonstrated effectiveness and advantages of DNA nanostructures as smart and targeted drug delivery systems or imaging agents within living organisms. In this review, we summarize the recent advances in structure design, cargo loading and cellular delivery of DNA nanocarriers, and discuss their potential in therapeutic applications.

scholarly journals Strategies to Build Hybrid Protein–DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1332
Author(s):  
Armando Hernandez-Garcia
Keyword(s):  
Dynamic Systems ◽  
Dna Nanotechnology ◽  
Chemical Properties ◽  
Hybrid Nanostructures ◽  
Advanced Materials ◽  
Dna Nanostructures ◽  
Hybrid Protein ◽  
Structural Protein ◽  
The Individual ◽  
Structural Dna Nanotechnology

Proteins and DNA exhibit key physical chemical properties that make them advantageous for building nanostructures with outstanding features. Both DNA and protein nanotechnology have growth notably and proved to be fertile disciplines. The combination of both types of nanotechnologies is helpful to overcome the individual weaknesses and limitations of each one, paving the way for the continuing diversification of structural nanotechnologies. Recent studies have implemented a synergistic combination of both biomolecules to assemble unique and sophisticate protein–DNA nanostructures. These hybrid nanostructures are highly programmable and display remarkable features that create new opportunities to build on the nanoscale. This review focuses on the strategies deployed to create hybrid protein–DNA nanostructures. Here, we discuss strategies such as polymerization, spatial directing and organizing, coating, and rigidizing or folding DNA into particular shapes or moving parts. The enrichment of structural DNA nanotechnology by incorporating protein nanotechnology has been clearly demonstrated and still shows a large potential to create useful and advanced materials with cell-like properties or dynamic systems. It can be expected that structural protein–DNA nanotechnology will open new avenues in the fabrication of nanoassemblies with unique functional applications and enrich the toolbox of bionanotechnology.

scholarly journals Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 1413
Author(s):  
Sofia Ojasalo ◽  
Petteri Piskunen ◽  
Boxuan Shen ◽  
Mauri A. Kostiainen ◽  
Veikko Linko
Keyword(s):  
Cell Activation ◽  
Immune Cell ◽  
Dna Nanotechnology ◽  
Biological Properties ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Nanoscale Structures ◽  
Immune Cell Activation ◽  
Wide Range ◽  
Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

scholarly journals Constructing Large 2D Lattices Out of DNA-Tiles

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1502
Author(s):  
Johannes M. Parikka ◽  
Karolina Sokołowska ◽  
Nemanja Markešević ◽  
J. Jussi Toppari
Keyword(s):  
Self Assembly ◽  
Dna Nanotechnology ◽  
Building Blocks ◽  
High Yield ◽  
Dna Nanostructures ◽  
Liquid Interfaces ◽  
Basic Principles ◽  
Dna Tiles ◽  
One Step ◽  
Solid Liquid

The predictable nature of deoxyribonucleic acid (DNA) interactions enables assembly of DNA into almost any arbitrary shape with programmable features of nanometer precision. The recent progress of DNA nanotechnology has allowed production of an even wider gamut of possible shapes with high-yield and error-free assembly processes. Most of these structures are, however, limited in size to a nanometer scale. To overcome this limitation, a plethora of studies has been carried out to form larger structures using DNA assemblies as building blocks or tiles. Therefore, DNA tiles have become one of the most widely used building blocks for engineering large, intricate structures with nanometer precision. To create even larger assemblies with highly organized patterns, scientists have developed a variety of structural design principles and assembly methods. This review first summarizes currently available DNA tile toolboxes and the basic principles of lattice formation and hierarchical self-assembly using DNA tiles. Special emphasis is given to the forces involved in the assembly process in liquid-liquid and at solid-liquid interfaces, and how to master them to reach the optimum balance between the involved interactions for successful self-assembly. In addition, we focus on the recent approaches that have shown great potential for the controlled immobilization and positioning of DNA nanostructures on different surfaces. The ability to position DNA objects in a controllable manner on technologically relevant surfaces is one step forward towards the integration of DNA-based materials into nanoelectronic and sensor devices.

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