Self-Limiting Polymerization of DNA Origami Subunits with Strain Accumulation

Abstract

Biology demonstrates how a near infinite array of complex systems and structures at many scales can originate from the self-assembly of component parts on the nanoscale. But to fully exploit the 2 benefits of self-assembly for nanotechnology, a crucial challenge remains: How do we rationally encode well-defined global architectures in subunits that are much smaller than their assemblies? Strain accumulation via geometric frustration is one mechanism that has been used to explain the self-assembly of global architectures in diverse and complex systems a posteriori. Here we take the next step and use strain accumulation as a rational design principle to control the length distributions of self-assembling polymers. We use the DNA origami method to design and synthesise a molecular subunit known as the PolyBrick, which perturbs its shape in response to local interactions via flexible allosteric blocking domains. These perturbations accumulate at the ends of polymers during growth, until the deformation becomes incompatible with further extension. We demonstrate that the key thermodynamic factors for controlling length distributions are the intersubunit binding free energy and the fundamental strain free energy, both which can be rationally encoded in a PolyBrick subunit. While passive polymerisation yields geometrical distributions, which have the highest statistical length uncertainty for a given mean, the PolyBrick yields polymers that approach Gaussian length distributions whose variance is entirely determined by the strain free energy. We also show how strain accumulation can in principle yield length distributions that become tighter with increasing subunit affinity and approach distributions with uniform polymer lengths. Finally, coarse-grained molecular dynamics and Monte Carlo simulations delineate and quantify the dominant forces influencing strain accumulation in a molecular system. This study constitutes a fundamental investigation of the use of strain accumulation as a rational design principle in molecular self-assembly.

A Primer on the oxDNA Model of DNA: When to Use it, How to Simulate it and How to Interpret the Results

“…Another significant application area for oxDNA has been the simulation of large structures to assess their conformation, stability and flexibility ( Fernandez-Castanon et al, 2016 ; Schreck et al, 2016 ; Sharma et al, 2017 ; Shi et al, 2017 ; Benson et al, 2018 ; Choi et al, 2018 ; Coronel et al, 2018 ; Berengut et al, 2019 ; Brady et al, 2019 ; Hoffecker et al, 2019 ; Snodin et al, 2019 ; Berengut et al, 2020 ; Chhabra et al, 2020 ; Poppleton et al, 2020 ; Tortora et al, 2020 ; Yao et al, 2020 ).…”

Mechanisms underlying sequence-dependent DNA hybridisation rates in the absence of secondary structure

“…Complementary DNA strands hybridise via Watson and Crick base pairing between A-T or G-C bases to form the DNA double helix or duplex (1), whose structural (2) and physical (3)(4)(5) properties are well characterised. In addition to its essential role in biology, DNA hybridisation also underpins DNA nanotechnology (6)(7)(8), which utilises DNA self-assembly for the construction of rationally designed nanoscale structures and machines (9)(10)(11)(12)(13)(14)(15)(16). DNA nanotechnology has led to the development of a broad range of technologies including applications in molecular sensing (17)(18)(19)(20), coordinating complex reaction cascades (21)(22)(23), drug delivery vessels (24)(25)(26)(27) and super resolution imaging methods, such as DNA points accumulation for imaging in nanoscale topography (DNA-PAINT) (28).…”

Characterizing the free-energy landscapes of DNA origamis

“…47 Moreover, the latest version of the model is able to accurately model the structural properties of DNA origami, 20 and so has been applied to study a wide range of different types of DNA origami. 21–23,38,61 Given the above, we are confident in using oxDNA to calculate the free-energy landscapes for our chosen DNA origamis, as detailed in the rest of this article.…”

“…Additionally, for origamis that are designed to assemble into higher-order structures, the monomer landscapes could help predict the thermodynamics of stress accumulation, particularly for examples where the stress accumulation is a design feature, for example, to make the assembly self-limiting. 38,39…”