Hierarchical assembly is more efficient than egalitarian assembly in synthetic capsids

The robust self-assembly of biological materials into large, but finite-size, superstructures is fundamental to life. However, competitive engineering approaches lag far behind. Here, we employ DNA origami patchy colloids designed to assemble into large capsids comprising 60 identical subunits. The individual building blocks have addressable interactions specified using a bioinspired lock-and-key mechanism with a tunable binding strength controlled to k_BT precision and with bond directionality determined to 2-3 degrees. Static light scattering is used as a non-invasive approach to quantify the inter-block association affinity in situ and to characterize the block-block association/disassociation rates. We consider assembly pathways that occur when all interparticle interactions are identical (egalitarian), and pathways in which subassemblies, e.g., dimers or pentamers, are preferred (hierarchical). Observations and modeling reveal that hierarchical assembly pathways in which the blocks first assemble into pentamers before further assembling into completed capsids are more efficient than egalitarian pathways with no preferred intermediate structure. This finding raises the question of whether hierarchical assembly is a general engineering principle for optimizing self-assembly of new materials that capture the remarkable functionalities found in living organisms.