Emergence by Design in Self-Assembling Protein Shells

Abstract

The use of proteins and peptides as nanoscale components to generate new-to-nature physical entities holds great promise in biocatalysis, therapeutic or diagnostic delivery, and materials templating. The majority of functional particles have been based on existing structures found in nature. Developing biomimetic particles in this way takes advantage of highly evolved platforms for organisation or encapsulation of functional moieties, offering significant advantages in stoichiometry, multivalency and sequestration. However, novel assembly paradigms for the modular construction of macromolecular structures is now greatly expanding the functional diversity of protein-based nanoparticles in health and manufacturing. Kepiro et al., in this issue of ACS Nano, demonstrate the refinement of this concept, engineering the capacity for self-assembly such that it is integral to pore-forming peptide motifs, resulting in superior antibiotic activity of the selfassembled particle. Nature encodes multiple functions in proteins with exquisite efficiency and emulating this multiplicity may be the ultimate goal of biomimetic nanotechnologies.

Conjugated Protein Domains as Engineered Scaffold Proteins

“…Additionally, integration of self-assembling properties results in behavior deviant from the isolated components, similarly to that observed within the described LLPS and hydrogel systems. Therefore, we envision future application of covalent scaffolds to template self-assembly, for example, in capsid formation , or in combination with other biomolecules such as RNA to study biomolecular condensate formation . Within these complex higher-order structures, modularity of these covalent scaffolds would allow for tunability of network formation.…”

Organelle-inspired supramolecular nanomedicine to precisely abolish liver tumor growth and metastasis

“…Owing to the advantages of peptides in bioactivity, ease of modification, and response to biological signals, self-assembling peptides have emerged as promising building blocks for the production of nanomaterials for drug delivery [ 14 , 15 ], bioimaging [ 16 , 17 ], and regenerative medicine [ 18 , 19 ]. Assisted by enzymes or small molecules in the cell milieu as stimuli to trigger peptide self-assembly, peptides may form self-adaptive architectures with spatiotemporal control, providing an ideal platform for creating biomimetic organelles [ 20 , 21 ]. Moreover, two or more successive bio-reactions in cells may confer cascade peptide self-assembly to implement precise size–shape control and efficient transportation of the resulting nanomaterials via pre-supposed self-assembly [ [22] , [23] , [24] ].…”

Dressing up artificial viral capsids self-assembled from C-terminal-modified β-annulus peptides

“…Moreover, an enzymatic reaction by horseradish peroxidase was encapsulated inside a capsid [11]. In addition to using natural protein nanocapsules, in recent years, chemical approaches for the rational design of artificial proteins [12][13][14][15][16][17][18][19][20][21][22] and peptides [12,13,[23][24][25][26][27][28][29][30] have been developed for the construction of self-assembled nanocapsules. The extension of molecular design to construct artificial protein/peptide nanocapsules would enhance the potential of such materials for application in a variety of areas and would particularly contribute to advances in the field of bio-nanotechnology.…”