The ability to allow dynamic assembly has begun to emerge as a new way to provide spatial and temporal control of material properties for improved efficacy ( 18). In parallel, new bioconjugation strategies are now available to provide controlled modifications of both the exterior and interior of protein nanostructures in benign conditions ( 17). Many well-known and de novo design noncovalent proteinвЂ“protein interaction pairs, such as coiled-coil domains, have been used to induce protein assembly to form distinct 3D nanostructures ( 16). In contrast, biological assembly tools have met with some notable success in engineering entirely new protein nanostructures ( 14, 15). The ability to combine multiple functionalities into a single protein nanostructure can help guide the desired localization and the preferred distribution of therapeutic agents to the disease site rather than healthy tissues ( 12).ДЄlthough rapid progress in chemical modifications has been made in the last decade, this strategy is still considered less attractive for the assembly of protein building blocks owing to lack of control of site selectivity and orientation, resulting in reduced bioactivity ( 13). The use of well-defined nanostructures is highly relevant for biomedical applications given the stringent demands for stability, biocompatibility, and biosafety. One of the more important contributions in recent years is the design of smart protein nano-assemblies for selectively targeting tissues for sensing and therapeutic applications ( 11). These tool kits have now been exploited to generate many synthetic protein architectures for different applications, such as catalysis, sensing, and biomedicine ( 9, 10). Synthetic biologists have taken inspiration from these native protein networks to develop modular protein assembly tool kits to create a broad spectrum of nanostructures ( 7, 8). For example, viral capsids are perfect examples of a highly optimized natural protein complex that forms a stable polyhedral structure for protecting, storing, and transporting viral genetic information ( 6).

Occasionally, additional functional and structural modules can be added through posttranslational modifications to expand the repertoire of functionalities ( 5). In some instances, protein nanostructures are formed through specific molecular interactions of their fundamental building blocks to properly coordinate complex functions such as biosynthesis, cell structure, and cellular communication ( 4). Proteins must work together to perform a variety of complex tasks ( 3). These architectures can provide critically needed improvements in biomedical applications, such as therapeutics and imaging, by enhancing the safety and efficacy of delivery vehicles. Such approaches have key appeal in medicine because of their capacity to generate well-controlled architectures with inherent biospecificity. Synthetic biology offers a powerful and streamlined platform for creating sophisticated, precisely organized nanostructures ( 2). These systems provide sizable improvements in bioavailability, cellular uptake, and reduced side effects, but a significant technology gap exists in the ability of carriers to both efficiently capture and release nucleic acids and other complex biopharmaceuticals, which comprise a rapidly increasing portion of the pharmaceutical pipeline. Over the past few decades, different synthetic carriers have been generated for these applications, fueled by advances in materials chemistry and nanotechnology ( 1). The development of effective therapeutic delivery vehicles and imaging reagents is of essential importance in medicine and healthcare.

Building blocks of proteins