[Paper Review] Numerical evidence for nucleated self-assembly of DNA brick origami

Aleks Reinhardt, Daan Frenkel|arXiv (Cornell University)|Feb 25, 2014

Advanced biosensing and bioanalysis techniques1 citations

TL;DR

This study uses Monte Carlo simulations to demonstrate that DNA brick origami can self-assemble into complex 3D structures like a cube with ~1000 distinct DNA strands through a nucleated process. The simulations show high-fidelity assembly within a narrow temperature window, where mis-assembly is disfavored due to a slow nucleation step, suggesting that complex structures can be achieved in other systems with proper design.

ABSTRACT

The observation by Ke et al. [Science 338, 1177 (2012)] that large numbers of short, pre-designed DNA strands can assemble into three-dimensional target structures came as a great surprise, as no colloidal self-assembling system has ever achieved the same degree of complexity. That failure seemed easy to rationalise: the larger the number of distinct building blocks, the higher the expected error rate for self-assembly. The experiments of Ke et al. have disproved this argument. Here, we report Monte Carlo simulations of the self-assembly of a DNA brick cube, comprising approximately 1000 types of DNA strand, using a simple model. We model the DNA strands as lattice tetrahedra with attractive patches, the interaction strengths of which are computed using a standard thermodynamic model. We find that, within a narrow temperature window, the target structure assembles with high probability. Our simulations suggest that mis-assembly is disfavoured because of a slow nucleation step. As our model incorporates no aspect of DNA other than its binding properties, these simulations suggest that, with proper design of the building blocks, other systems, such as colloids, may also assemble into truly complex structures.

Motivation & Objective

• To investigate the mechanism enabling high-fidelity self-assembly of complex DNA brick structures with ~1000 distinct strands.
• To challenge the assumption that increasing the number of distinct building blocks inevitably raises error rates in self-assembly.
• To determine whether nucleation dynamics play a key role in suppressing mis-assembly in complex systems.
• To explore whether the principles observed in DNA brick self-assembly could be generalized to other systems like colloids.

Proposed method

• Monte Carlo simulations were used to model the self-assembly of a DNA brick cube composed of approximately 1000 distinct DNA strands.
• DNA strands were represented as lattice tetrahedra with specific attractive patches to simulate binding interactions.
• Interaction strengths between patches were computed using a standard thermodynamic model to reflect DNA hybridization energetics.
• The simulations explored assembly outcomes across a range of temperatures to identify conditions favoring target structure formation.
• The model excluded structural details beyond binding properties, focusing solely on thermodynamic and kinetic aspects of assembly.
• Assembly pathways were analyzed to assess nucleation rates and mis-assembly probabilities.

Experimental results

Research questions

• RQ1 Can a system with ~1000 distinct DNA strands self-assemble into a defined 3D structure with high fidelity?
• RQ2 Is the slow nucleation step responsible for disfavoring mis-assembly in complex DNA brick systems?
• RQ3 Does a narrow temperature window exist where target structure formation is significantly favored over errors?
• RQ4 Can the principles of DNA brick self-assembly be extended to other programmable materials like colloids?

Key findings

• The target DNA brick cube assembled with high probability within a narrow temperature window, indicating a specific regime of optimal self-assembly conditions.
• Mis-assembly was disfavored due to a slow nucleation step, which reduced the likelihood of incorrect structures forming.
• The simulations demonstrated that high complexity does not inherently lead to high error rates when nucleation is kinetically controlled.
• The absence of structural details in the model suggests that binding properties alone are sufficient to enable complex self-assembly.
• The findings imply that other systems, such as colloids, could achieve similar complexity if their components are properly designed.