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 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 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.

scholarly journals DNA nanotechnology approaches for microRNA detection and diagnosis

2019 ◽  
Vol 47 (20) ◽  
pp. 10489-10505 ◽  
Author(s):  
Arun Richard Chandrasekaran ◽  
Jibin Abraham Punnoose ◽  
Lifeng Zhou ◽  
Paromita Dey ◽  
Bijan K Dey ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Origami ◽  
Great Promise ◽  
Dna Nanostructures ◽  
New Class ◽  
Advantages And Disadvantages ◽  
Critical Comparison ◽  
Microrna Detection ◽  
Disease Diagnostics ◽  
Detection And Diagnosis

Abstract MicroRNAs are involved in the crucial processes of development and diseases and have emerged as a new class of biomarkers. The field of DNA nanotechnology has shown great promise in the creation of novel microRNA biosensors that have utility in lab-based biosensing and potential for disease diagnostics. In this Survey and Summary, we explore and review DNA nanotechnology approaches for microRNA detection, surveying the literature for microRNA detection in three main areas of DNA nanostructures: DNA tetrahedra, DNA origami, and DNA devices and motifs. We take a critical look at the reviewed approaches, advantages and disadvantages of these methods in general, and a critical comparison of specific approaches. We conclude with a brief outlook on the future of DNA nanotechnology in biosensing for microRNA and beyond.

scholarly journals The Art of Designing DNA Nanostructures with CAD Software

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2287
Author(s):  
Martin Glaser ◽  
Sourav Deb ◽  
Florian Seier ◽  
Amay Agrawal ◽  
Tim Liedl ◽  
...  
Keyword(s):  
Human Error ◽  
Dna Nanotechnology ◽  
Holliday Junctions ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Dna Structures ◽  
Current State ◽  
Software Packages ◽  
Wide Range ◽  
Time Required

Since the arrival of DNA nanotechnology nearly 40 years ago, the field has progressed from its beginnings of envisioning rather simple DNA structures having a branched, multi-strand architecture into creating beautifully complex structures comprising hundreds or even thousands of unique strands, with the possibility to exactly control the positions down to the molecular level. While the earliest construction methodologies, such as simple Holliday junctions or tiles, could reasonably be designed on pen and paper in a short amount of time, the advent of complex techniques, such as DNA origami or DNA bricks, require software to reduce the time required and propensity for human error within the design process. Where available, readily accessible design software catalyzes our ability to bring techniques to researchers in diverse fields and it has helped to speed the penetration of methods, such as DNA origami, into a wide range of applications from biomedicine to photonics. Here, we review the historical and current state of CAD software to enable a variety of methods that are fundamental to using structural DNA technology. Beginning with the first tools for predicting sequence-based secondary structure of nucleotides, we trace the development and significance of different software packages to the current state-of-the-art, with a particular focus on programs that are open source.

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.

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 Minimizing Cholesterol-Induced Aggregation of Membrane-Interacting DNA Origami Nanostructures

Membranes ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 950
Author(s):  
Jasleen Kaur Daljit Singh ◽  
Minh Tri Luu ◽  
Jonathan F. Berengut ◽  
Ali Abbas ◽  
Shelley F. J. Wickham ◽  
...  
Keyword(s):  
Dna Nanotechnology ◽  
Dna Origami ◽  
Second Step ◽  
Dna Nanostructures ◽  
Spacer Length ◽  
Modified Dna ◽  
Functional Membrane ◽  
Cholesterol Control ◽  
2D And 3D ◽  
Induced Aggregation

DNA nanotechnology provides methods for building custom membrane-interacting nanostructures with diverse functions, such as shaping membranes, tethering defined numbers of membrane proteins, and transmembrane nanopores. The modification of DNA nanostructures with hydrophobic groups, such as cholesterol, is required to facilitate membrane interactions. However, cholesterol-induced aggregation of DNA origami nanostructures remains a challenge. Aggregation can result in reduced assembly yield, defective structures, and the inhibition of membrane interaction. Here, we quantify the assembly yield of two cholesterol-modified DNA origami nanostructures: a 2D DNA origami tile (DOT) and a 3D DNA origami barrel (DOB), by gel electrophoresis. We found that the DOT assembly yield (relative to the no cholesterol control) could be maximised by reducing the number of cholesterols from 6 to 1 (2 ± 0.2% to 100 ± 2%), optimising the separation between adjacent cholesterols (64 ± 26% to 78 ± 30%), decreasing spacer length (38 ± 20% to 95 ± 5%), and using protective ssDNA 10T overhangs (38 ± 20% to 87 ± 6%). Two-step folding protocols for the DOB, where cholesterol strands are added in a second step, did not improve the yield. Detergent improved the yield of distal cholesterol configurations (26 ± 22% to 92 ± 12%), but samples re-aggregated after detergent removal (74 ± 3%). Finally, we confirmed functional membrane binding of the cholesterol-modified nanostructures. These findings provide fundamental guidelines to reducing the cholesterol-induced aggregation of membrane-interacting 2D and 3D DNA origami nanostructures, improving the yield of well-formed structures to facilitate future applications in nanomedicine and biophysics.

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.

Multiform DNA origami arrays using minimal logic control

Nanoscale ◽  
2020 ◽  
Vol 12 (28) ◽  
pp. 15066-15071 ◽  
Author(s):  
Congzhou Chen ◽  
Jin Xu ◽  
Xiaolong Shi
Keyword(s):  
Dna Nanotechnology ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Minimal Logic ◽  
Logic Control ◽  
Self Assembled

Self-assembled DNA nanostructures significantly contribute to DNA nanotechnology.

scholarly journals Free energy landscape of salt-actuated reconfigurable DNA nanodevices

2019 ◽  
Vol 48 (2) ◽  
pp. 548-560
Author(s):  
Ze Shi ◽  
Gaurav Arya
Keyword(s):  
Free Energy ◽  
Energy Barrier ◽  
Energy Landscape ◽  
Critical Role ◽  
Dna Nanotechnology ◽  
Dna Origami ◽  
Free Energy Landscape ◽  
Dna Structures ◽  
Closed State ◽  
Underlying Basis

Abstract Achieving rapid, noninvasive actuation of DNA structures is critical to expanding the functionality of DNA nanotechnology. A promising actuation approach involves introducing multiple, short pairs of single-stranded DNA overhangs to components of the structure and triggering hybridization or dissociation of the overhangs via changes in solution ionic conditions to drive structural transitions. Here, we reveal the underlying basis of this new approach by computing via molecular simulations the free energy landscape of DNA origami hinges actuated between open and closed states. Our results reveal how the overhangs collectively introduce a sharp free-energy minimum at the closed state and a broad energy barrier between open and closed states and how changes in ionic conditions modulate these features of the landscape to drive actuation towards the open or closed state. We demonstrate the critical role played by hinge confinement in stabilizing the hybridized state of the overhangs and magnifying the energy barrier to dissociation. By analyzing how the distribution of overhangs and their length and sequence modulate the energy landscape, we obtain design rules for tuning the actuation behavior. The molecular insights obtained here should be applicable to a broad range of systems involving DNA hybridization within confined systems.

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