Controlled Self-Assembly of Proteins into Discrete Nanoarchitectures Templated by Gold Nanoparticles via Monovalent Interfacial Engineering

Abstract

Designed rational assembly of proteins promises novel properties and functionalities as well as new insights into the nature of life. <i>De novo</i> design of artificial protein nanostructures has been achieved using protein subunits or peptides as building blocks. However, controlled assembly of protein nanostructures into higher-order discrete nanoarchitectures, rather than infinite arrays or aggregates, remains a challenge due to the complex or symmetric surface chemistry of protein nanostructures. Here we develop a facile strategy to control the hierarchical assembly of protein nanocages into discrete nanoarchitectures with gold nanoparticles (AuNPs) as scaffolds via rationally designing their interfacial interaction. The protein nanocage is monofunctionalized with a polyhistidine tag (Histag) on the external surface through a mixed assembly strategy, while AuNPs are modified with Ni²⁺−NTA chelates, so that the protein nanocage can controllably assemble onto the AuNPs via the Histag−Ni²⁺ affinity. Discrete protein nanoarchitectures with tunable composition can be generated by stoichiometric control over the ratio of protein nanocage to AuNP or change of AuNP size. The methodology described here is extendable to other protein nanostructures and chemically synthesized nanomaterials, and can be borrowed by synthetic biology for biomacromolecule manipulation