Elucidating the Mechanical Energy for Cyclization of a DNA Origami Tile

Abstract

DNA origami has emerged as a versatile method to synthesize nanostructures with high precision. This bottom-up self-assembly approach can produce not only complex static architectures, but also dynamic reconfigurable structures with tunable properties. While DNA origami has been explored increasingly for diverse applications such as biomedical and biophysical tools, related mechanics are also under active investigation. Here we studied the structural properties of DNA origami and investigated the energy needed to deform the DNA structures. We used a single-layer rectangular DNA origami tile as a model system and studied its cyclization process. This origami tile was designed with an inherent twist by placing crossovers every 16 base-pairs (bp), corresponding to a helical pitch of 10.67 bp/turn which is slightly different from that of native B-form DNA (10.5 bp/turn). We used molecular dynamics (MD) simulations based on a coarse-grained model on an open-source computational platform, oxDNA. We calculated the energies needed to overcome the initial curvature and induce mechanical deformation by applying linear spring forces. We found that the initial curvature may be overcome gradually during cyclization and a total of ~33.1 kcal/mol is required to complete the deformation. These results provide insights into the DNA origami mechanics and should be useful for diverse applications such as adaptive reconfiguration and energy absorption.

Planar 2D wireframe DNA origami

“…However, because these 2D origami objects are visualized nearly exclusively on 2D surfaces using atomic force microscopy (AFM) or transmission electron microscopy (TEM), objects typically appear flat despite their curvature, bend, or twist in 3D solution (3)(4)(5). Although 3D structure prediction tools such as CanDo (6) have been used to reduce out-of-plane deformations (7)(8)(9), experimental validation of planarity has remained elusive, together with general design rules to attain and maintain planarity for arbitrary 2D geometries. While there have been several attempts to both study and control the planarity of 2D DNA origami rendered with single-layer parallel duplexes in recent years (10,11), resolving the 3D structure of these assemblies in solution has remained elusive, likely because of their flexibility and heterogeneity in solution, corroborated by solution scattering data (10) and AFM (11).…”

“…While experimentally elusive to realize and validate, planarity of 2D origami is of paramount importance to numerous applications that seek to organize secondary materials with nanometer-scale precision (13,14), including fundamental studies of light harvesting and excitonics (15)(16)(17)(18), single-molecule (19)(20)(21) and superresolution imaging (19,22), molecular biophysics (23), photonics (24), cellular biophysics (25)(26)(27)(28), and surface-based patterning and lithography (29,30). Multilayer honeycomb (31) and square lattice (32) bricklike origami designs offer alternatives to fabricating monolayer 2D origami, but they achieve planarity while reducing the overall lateral dimension of objects that can be rendered because of the increased length of scaffold required; they may require careful sequence design with iterative feedback from structural simulations and experiment to reduce or eliminate intrinsic twist (6,8,9,32), and they are largely limited geometrically to rendering rectilinear geometries that consist of parallel duplexes throughout the object, with (33) or without curvature (1,34). Attaching 2D monolayer origami to surfaces using high-affinity ligand-receptor pairs may be used to partially flatten objects, although experimental validation is again challenging because of the perturbative nature of AFM and the low contrast of TEM, and numerous applications are not amenable to this biochemical immobilization strategy.…”

Salt-induced conformational switching of a flat rectangular DNA origami structure

“…18 Generally, the dynamic flexibility of DNA origami structures is difficult to access as structural tools usually yield average values and dynamic, little invasive tools are required including optical 10,[12][13][14][15] and mechanical singlemolecule methods [19][20][21] as well as computational tools such as molecular dynamics simulations. 22 The rectangular DNA origami structure of the original Rothemund publication 1 and its torsion-reduced variants such as the so-called new rectangular origami (NRO) 23 have emerged as model systems to interrogate the stiffness and dynamics of a 2D nucleic acid structure. 22,24,25 Recent oxDNA 26 simulations indicated that the NRO exhibits substantial structural dynamics and tends to dynamically twist along the two diagonal axes.…”

“…22 The rectangular DNA origami structure of the original Rothemund publication 1 and its torsion-reduced variants such as the so-called new rectangular origami (NRO) 23 have emerged as model systems to interrogate the stiffness and dynamics of a 2D nucleic acid structure. 22,24,25 Recent oxDNA 26 simulations indicated that the NRO exhibits substantial structural dynamics and tends to dynamically twist along the two diagonal axes. 27 It has also been shown that NROs can roll up and form tubes when strands protruding from one long edge hybridize to strands protruding from the opposite long axis edge.…”

“…18 Generally, the dynamic flexibility of DNA origami structures is difficult to access as structural tools usually yield average values and dynamic, little invasive tools are required including optical 10,12–15 and mechanical single-molecule methods 19–21 as well as computational tools such as molecular dynamics simulations. 22…”