Direct observation and rational design of nucleation behavior in addressable self-assembly

TL;DR

This study combines experiments and simulations to understand and control nucleation pathways in DNA-brick self-assembly, enabling optimized assembly conditions through rational design of nucleation barriers.

Contribution

It introduces a combined experimental and computational approach to elucidate and manipulate nucleation pathways in addressable self-assembly, demonstrating how small modifications can enhance assembly yield.

Findings

Stable multi-subunit clusters lower nucleation barriers.

Modified structures increase the range of successful assembly conditions.

Experimental results agree well with coarse-grained simulation predictions.

Abstract

In order to optimize a self-assembly reaction, it is essential to understand the factors that govern its pathway. Here, we examine the influence of nucleation pathways in a model system for addressable, multicomponent self-assembly based on a prototypical 'DNA-brick' structure. By combining temperature-dependent dynamic light scattering and atomic force microscopy with coarse-grained simulations, we show how subtle changes in the nucleation pathway profoundly affect the yield of the correctly formed structures. In particular, we can increase the range of conditions over which self-assembly occurs by utilizing stable multi-subunit clusters that lower the nucleation barrier for assembling subunits in the interior of the structure. Consequently, modifying only a small portion of a structure is sufficient to optimize its assembly. Due to the generality of our coarse-grained model and the excellent agreement that we find with our experimental results, the design principles reported here are likely to apply generically to addressable, multicomponent self-assembly.