Viruses and virus-like protein assemblies—Chemically programmable nanoscale building blocks

Abstract

Supramolecular proteins are generated using a limited set of twenty amino acids, but have distinctive functionalities which arise from the sequential arrangement of amino acids configured to exquisite threedimensional structures. Viruses, virus-like particles, ferritins, enzyme complexes, cellular micro-compartments, and other supramolecular protein assemblies exemplify these systems, with their precise arrangements of tens to hundreds of molecules into highly organized scaffolds for nucleic acid packaging, metal storage, catalysis or sequestering reactions at the nanometer scale. These versatile protein systems, dubbed as bionanoparticles (BNPs), have attracted materials scientists to seek new opportunities with these pre-fabricated templates in a wide range of nanotechnology-related applications. Here, we focus on some of the key modifi cation strategies that have been utilized, ranging from basic protein conjugation techniques to more novel strategies, to expand the functionalities of these multimeric protein assemblies. Ultimately, in combination with molecular cloning and sophisticated chemistries, these BNPs are being incorporated into many applications ranging from functional materials to novel biomedical drug designs.

Polymer Directed Protein Assemblies

“…Virus particles in general are attractive protein-based particles which show great promise in bionanotechnology, as they have been used as, e.g., delivery vessel, templates, nanowires, liquid crystals [69][70][71]. It is only natural that virus particles are combined with polymers, not only in a non-covalent fashion as described above but also covalently.…”

His-tagged norovirus-like particles: A versatile platform for cellular delivery and surface display

“…In the field of gene and immune therapy, VLP-based tools have been developed by modulating VLP packaging, display, and/or targeting (reviewed extensively, for example, in [3][4][5][6][7]). Furthermore, VLPs even show promise as new biological nanomaterials [8][9][10][11][12]. As a nanocarrier platform, VLPs offer the advantages of morphological uniformity, biocompatibility, the capacity to potentiate the immune response, and easy functionalization.…”

Crosslinking of viral nanoparticles with “clickable” fluorescent crosslinkers at the interface

“…Of all the reactions that can be ranked under click chemistry, Cu(I) catalyzed alkyne-azide cycloaddition (CuAAC) reaction is undoubtedly the premier example of all [4,5]. This reaction has been extensively used in materials development [6][7][8][9], polymer synthesis [10,11], dendrimer synthesis [12][13][14][15][16] and drug discovery [17][18][19]. CuAAC reaction serves as a great tool for bioconjugation applications [20][21][22][23][24][25][26][27][28][29], mainly due to (i) facile synthesis and easy incorporation of alkyne and azide moieties into biomolecular frameworks, (ii) compatibility to other functionalities yielding highly specific products, (iii) compatibility to water which is crucial for biomolecular systems, (iv) mild reaction conditions which will help maintaining the properties of biomolecules, and (v) stability of the resulting triazole ring to the hydrolytic cleavage, oxidation and reduction [2,3,9].…”

“…A plant virus, turnip yellow mosaic virus (TYMV), was used as the model to demonstrate the reaction potential of these dyes in crosslinking two particles. Recent studies indicate that TYMV can be employed as a great tool in drug delivery, imaging and tissue engineering applications [6,[42][43][44][45][46]. This symmetric bionanoparticle (BNP) could self-assemble at the liquid-liquid interface to yield stable emulsion systems and highly ordered long range arrays at the flat interface [44].…”