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.

Structural DNA nanotechnology: Immobile Holliday junctions to artificial robots

2022 ◽  
Vol 22 ◽  
Author(s):  
Raghu Pradeep Narayanan ◽  
Leeza Abraham
Keyword(s):  
Dna Nanotechnology ◽  
Building Blocks ◽  
Holliday Junctions ◽  
Dna Origami ◽  
Building Structures ◽  
Dna Nanostructures ◽  
3 Dimensional ◽  
Scientific World ◽  
2D And 3D ◽  
Structural Dna Nanotechnology

Abstreact: DNA nanotechnology marvels the scientific world with its capabilities to design, engineer, and demonstrate nanoscale shapes. This review is a condensed version walking the reader through the structural developments in the field over the past 40 years starting from the basic design rules of the double-stranded building block to the most recent advancements in self-assembled hierarchically achieved structures to date. It builds off from the fundamental motivation of building 3-dimensional (3D) lattice structures of tunable cavities going all the way up to artificial nanorobots fighting cancer. The review starts by covering the most important developments from the fundamental bottom-up approach of building structures, which is the ‘tile’ based approach covering 1D, 2D, and 3D building blocks, after which, the top-down approach using DNA origami and DNA bricks is also covered. Thereafter, DNA nanostructures assembled using not so commonly used (yet promising) techniques like i-motifs, quadruplexes, and kissing loops are covered. Highlights from the field of dynamic DNA nanostructures have been covered as well, walking the reader through the various approaches used within the field to achieve movement. The article finally concludes by giving the authors a view of what the future of the field might look like while suggesting in parallel new directions that fellow/future DNA nanotechnologists could think about.

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 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.

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 Unraveling the interaction between doxorubicin and DNA origami nanostructures for customizable chemotherapeutic drug release

2020 ◽  
Author(s):  
Heini Ijäs ◽  
Boxuan Shen ◽  
Amelie Heuer-Jungemann ◽  
Adrian Keller ◽  
Mauri A. Kostiainen ◽  
...  
Keyword(s):  
Drug Release ◽  
Targeted Delivery ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Base Pairs ◽  
Experimental Conditions ◽  
Spectral Changes ◽  
Dna Binding Affinity ◽  
2D And 3D ◽  
Release Profiles

ABSTRACTDoxorubicin (DOX) is a common drug in cancer chemotherapy, and its high DNA-binding affinity can be harnessed in preparing DOX-loaded DNA nanostructures for targeted delivery and therapeutics. Although DOX has been widely studied, the existing literature of DOX-loaded DNA nanocarriers remains limited and incoherent. Here, based on an in-depth spectroscopic analysis, we characterize and optimize the DOX loading into different 2D and 3D scaffolded DNA origami nanostructures (DONs). In our experimental conditions, all DONs show similar DOX binding capacities (one DOX molecule per two to three base pairs), and the binding equilibrium is reached within seconds, remarkably faster than previously acknowledged. To characterize customizable drug release profiles, DON degradation and DOX release from the complexes upon DNase I digestion was studied. For the employed DONs, the relative doses (DOX molecules released per unit time) may vary by two orders of magnitude depending on the DON superstructure. In addition, we identify DOX aggregation mechanisms and spectral changes linked to pH, magnesium, and DOX concentration. This has been largely ignored in experimenting with DNA nanostructures, but is probably a major source of the incoherence of the experimental results so far. Therefore, we believe this work can act as a guide to tailoring the release profiles and developing better drug delivery systems based on DNA carriers.

scholarly journals Controlling aggregation of cholesterol-modified DNA nanostructures

2019 ◽  
Vol 47 (21) ◽  
pp. 11441-11451 ◽  
Author(s):  
Alexander Ohmann ◽  
Kerstin Göpfrich ◽  
Himanshu Joshi ◽  
Rebecca F Thompson ◽  
Diana Sobota ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Lipid Membranes ◽  
Structural Control ◽  
Polyacrylamide Gel Electrophoresis ◽  
Dna Nanotechnology ◽  
Dna Nanostructures ◽  
Hydrophobic Moiety ◽  
Modified Dna ◽  
Dynamics Simulations

Abstract DNA nanotechnology allows for the design of programmable DNA-built nanodevices which controllably interact with biological membranes and even mimic the function of natural membrane proteins. Hydrophobic modifications, covalently linked to the DNA, are essential for targeted interfacing of DNA nanostructures with lipid membranes. However, these hydrophobic tags typically induce undesired aggregation eliminating structural control, the primary advantage of DNA nanotechnology. Here, we study the aggregation of cholesterol-modified DNA nanostructures using a combined approach of non-denaturing polyacrylamide gel electrophoresis, dynamic light scattering, confocal microscopy and atomistic molecular dynamics simulations. We show that the aggregation of cholesterol-tagged ssDNA is sequence-dependent, while for assembled DNA constructs, the number and position of the cholesterol tags are the dominating factors. Molecular dynamics simulations of cholesterol-modified ssDNA reveal that the nucleotides wrap around the hydrophobic moiety, shielding it from the environment. Utilizing this behavior, we demonstrate experimentally that the aggregation of cholesterol-modified DNA nanostructures can be controlled by the length of ssDNA overhangs positioned adjacent to the cholesterol. Our easy-to-implement method for tuning cholesterol-mediated aggregation allows for increased control and a closer structure–function relationship of membrane-interfacing DNA constructs — a fundamental prerequisite for employing DNA nanodevices in research and biomedicine.

Chemical ligation of an entire DNA Origami nanostructure

Nanoscale ◽  
2021 ◽  
Author(s):  
Nicole Weizenmann ◽  
Gerda Scheidgen-Kleyboldt ◽  
Jingjing Ye ◽  
Cordula Bärbel Krause ◽  
Dominik Kauert ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Dna Nanotechnology ◽  
Dna Origami ◽  
Dna Nanostructures ◽  
Chemical Ligation

Within the field of DNA nanotechnology, numerous methods were developed to produce complex two- and three-dimensional DNA nanostructures for many different emerging applications. These structures typically suffer from a low...

scholarly journals Generating DNA Origami Nanostructures through Shape Annealing

2021 ◽  
Vol 11 (7) ◽  
pp. 2950
Author(s):  
Bolutito Babatunde ◽  
D. Sebastian Arias ◽  
Jonathan Cagan ◽  
Rebecca E. Taylor
Keyword(s):  
Self Assembly ◽  
Design Space ◽  
Simulated Annealing Algorithm ◽  
Dna Nanotechnology ◽  
Dna Origami ◽  
Design Tools ◽  
Dna Nanostructures ◽  
Formal Approach ◽  
Annealing Algorithm ◽  
Structural Dna Nanotechnology

Structural DNA nanotechnology involves the design and self-assembly of DNA-based nanostructures. As a field, it has progressed at an exponential rate over recent years. The demand for unique DNA origami nanostructures has driven the development of design tools, but current CAD tools for structural DNA nanotechnology are limited by requiring users to fully conceptualize a design for implementation. This article introduces a novel formal approach for routing the single-stranded scaffold DNA that defines the shape of DNA origami nanostructures. This approach for automated scaffold routing broadens the design space and generates complex multilayer DNA origami designs in an optimally driven way, based on a set of constraints and desired features. This technique computes unique designs of DNA origami assemblies by utilizing shape annealing, which is an integration of shape grammars and the simulated annealing algorithm. The results presented in this article illustrate the potential of the technique to code desired features into DNA nanostructures.

Sign in / Sign up

Export Citation Format

Share Document