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. 2016 Jul 25;55(31):8869-72.
doi: 10.1002/anie.201602446. Epub 2016 Jun 15.

Computer-Aided Production of Scaffolded DNA Nanostructures From Flat Sheet Meshes

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Free PMC article

Computer-Aided Production of Scaffolded DNA Nanostructures From Flat Sheet Meshes

Erik Benson et al. Angew Chem Int Ed Engl. .
Free PMC article

Abstract

The use of DNA as a nanoscale construction material has been a rapidly developing field since the 1980s, in particular since the introduction of scaffolded DNA origami in 2006. Although software is available for DNA origami design, the user is generally limited to architectures where finding the scaffold path through the object is trivial. Herein, we demonstrate the automated conversion of arbitrary two-dimensional sheets in the form of digital meshes into scaffolded DNA nanostructures. We investigate the properties of DNA meshes based on three different internal frameworks in standard folding buffer and physiological salt buffers. We then employ the triangulated internal framework and produce four 2D structures with complex outlines and internal features. We demonstrate that this highly automated technique is capable of producing complex DNA nanostructures that fold with high yield to their programmed configurations, covering around 70 % more surface area than classic origami flat sheets.

Keywords: DNA origami; DNA structures; atomic force microscopy; molecular simulation.

Figures

Figure 1
Figure 1
Example pipeline for the production of a 2D DNA structure from a mesh. A) First, an arbitrarily sized mesh (gray) is created in a 3D graphics software program. From this canvas, the desired mesh (red) is produced by deleting the extra edges and vertices. B) The edges and vertices of the mesh can then be remodeled to create the desired shape. C) An uninterrupted scaffold path through the mesh is then found algorithmically. D) A physical simulation where the DNA helices are represented by rigid cylinders connected by springs is used to generate a DNA model with minimized internal tension. E) This DNA model is imported to vHelix where the final DNA staple design and sequences are generated.
Figure 2
Figure 2
DNA 2D sheets based on regular tessellations. A) Internal frameworks of DNA 2D structures based on the 6‐tesselation (left), 4‐tesselation (center), and 3‐tesselation (right). Insets: full design structures (drawn to scale). B) 2×2 μm field‐of‐view AFM images of the structures folded with 10 mm MgCl2. C, D) 250×250 nm AFM images of the structures folded with 10 mm MgCl2 buffer (C) or PBS (D). E) 100×40 nm expanded portions of areas marked by boxes in (D). F) Histograms, with data measured from AFM images, where the x‐axis is area per base pair measured in nm2 and the y‐axis shows the number of structures (n). Additional data provided in Figure S5 and Table S1. All scale bars=100 nm.
Figure 3
Figure 3
2D sheets based on a triangulated mesh. A) A ring with an inner diameter of 80 nm. B) A three‐hole disc with a diameter of 120 nm. C) A hand‐shaped mesh. D) A mesh shape with an outline representing Norway, Sweden, and Finland. Middle row: 2×2 μm field‐of‐view AFM images of the structures. Bottom row: 200×200 nm AFM images of the structures. All scale bars=100 nm.

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