Bioinspired Approaches to Self-Assembly of Virus-like Particles: From Molecules to Materials

ConspectusWhen viewed through the lens of materials science, nature provides a vast library of hierarchically organized structures that serve as inspiration and raw materials for new synthetic materials. The structural organization of complex bioarchitectures with advanced functions arises from the association of building blocks and is strongly supported by ubiquitous mechanisms of self-assembly, where interactions among components result in spontaneous assembly into defined structures. Viruses are exemplary, where a capsid structure, often formed from the self-assembly of many individual protein subunits, serves as a vehicle for the transport and protection of the viral genome. Higher-order assemblies of viral particles are also found in nature with unexpected collective behaviors. When the infectious aspect of viruses is removed, the self-assembly of viral particles and their potential for hierarchical assembly become an inspiration for the design and construction of a new class of functional materials at a range of different length scales.Salmonella typhimurium bacteriophage P22 is a well-studied model for understanding viral self-assembly and the construction of virus-like particle (VLP)-based materials. The formation of cage-like P22 VLP structures results from scaffold protein (SP)-directed self-assembly of coat protein (CP) subunits into icosahedral capsids with encapsulation of SP inside the capsid. Employing the CP−SP interaction during self-assembly, the encapsulation of guest protein cargos inside P22 VLPs can be achieved with control over the composition and the number of guest cargos. The morphology of cargo-loaded VLPs can be altered, along with changes in both the physical properties of the capsid and the cargo–capsid interactions, by mimicking aspects of the infectious P22 viral maturation. The structure of the capsid differentiates the inside cavity from the outside environment and serves as a protecting layer for the encapsulated cargos. Pores in the capsid shell regulate molecular exchange between inside and outside, where small molecules can traverse the capsid freely while the diffusion of larger molecules is limited by the pores. The interior cavity of the P22 capsid can be packed with hundreds of copies of cargo proteins (especially enzymes), enforcing intermolecular proximity, making this an ideal model system in which to study enzymatic catalysis in crowded and confined environments. These aspects highlight the development of functional nanomaterials from individual P22 VLPs, through biomimetic design and self-assembly, resulting in fabrication of nanoreactors with controlled catalytic behaviors.Individual P22 VLPs have been used as building blocks for the self-assembly of higher-order structures. This relies on a balance between the intrinsic interparticle repulsion and a tunable interparticle attraction. The ordering of VLPs within three-dimensional assemblies is dependent on the balance between repulsive and attractive interactions: too strong an attraction results in kinetically trapped disordered structures, while decreasing the attraction can lead to more ordered arrays. These higher-order assemblies display collective behavior of high charge density beyond those of the individual VLPs.The development of synthetic nanomaterials based on P22 VLPs demonstrates how the potential for hierarchical self-assembly can be applied to other self-assembling capsid structures across multiple length scales toward future bioinspired functional materials.