Assembly kinetics of synthetic capsids made from DNA origami*

The robust self-assembly of biological materials into large, but finite-size, superstructures is fundamental to life. One of the prototypical examples is a virus capsid, whose widely various geometries are built from either a single or a few species of repeating units. Inspired by this efficient paradigm, we previously developed a programmable engineering analog composed of user-prescribed DNA origami subunits. While the equilibrium structure of the synthetic capsid was determined, the dynamical transformation from a disorganized state of individual building blocks into an ordered state of a fully-closed capsid shell remains uncharacterized. To reveal the underlying mechanism, we firstly undertake a quantitative study of the on- and off- rates of the monomer-dimer transition as a function of interaction strength. Specifically, the inter-block lock-and-key docking with base-stacking plus variable hybridizations enables precise control of binding strength. We utilize static and dynamic light scattering to quantify the association affinity in situ and non-invasively monitor the assembly kinetics. With the knowledge thus gained, we aim to realize assembly of various artificial capsids with optimized yield and reaction time.