Biomimetic Structural Proteins: Modular Assembly and High Mechanical Performance

Protein-based biomaterials attract growing interests due to their encoded and programmable robust mechanical properties, superelasticity, plasticity, shape adaptability, excellent interfacial behavior, etc., derived from sequence-guided backbone structures, particularly compared to chemically synthetic counterparts in materials science and biomedical engineering. For example, protein materials have been successfully fabricated as (1) artificial implants (man-made tendons, cartilages, or dental tissues), due to programmable chemistry and biocompatibility; (2) smart biodevices with temperature/light-response and self-healing effects; and (3) impact resistance materials having great mechanical performance due to biomimetics. However, the existing method of regenerating protein materials from natural sources has two critical issues, low yield and structural damage, making it unable to meet demands. Therefore, it is crucial to develop an alternative strategy for fabricating protein materials. Heterologous expression of natural proteins with a modular assembly approach is an effective strategy for material preparation. Standardized, easy-to-assemble protein modules with specific structures and functions are developed through experimental and computational tools based on natural functional protein sequences. Through recombination and heterologous expression, these artificial protein modules become keys to material fabrication. Undergoing an assembly process similar to supramolecular self-assembly of proteins in cells, biomimetic modules can be fabricated for formation of macroscopic materials such as fibers and adhesives. This strategy inspired by synthetic biology and supramolecular chemistry is important for improving target protein yields and assembly integrity. It also preserves and optimizes the mechanical functions of structural proteins, accelerating the design and fabrication of artificial protein materials.In this Account, we overview recent studies on fabricating biomimetic protein materials to elucidate the concept of modular assembly. We discuss the design of biomimetic structural proteins at the molecular level, providing a wealth of details determining the bulk properties of materials. Additinally, we describe the modular self-assembly and assembly driven by inducing molecules, and mechanical properties and applications of resulting fibers. We used these strategies to develop fiber materials with high tensile strength, high toughness, and properties such as anti-icing and high-temperature resistance. We also extended this approach to design protein-based adhesives with ultra-strong adhesion, biocompatibility, and biodegradability for surgical applications such as wound sealing and healing. Other protein materials, including films and hydrogels, have been developed through chemical assembly routes. Finally, we describe exploiting synthetic biology and chemistry to overcome bottlenecks in structural protein modular design, biosynthesis, and material assembly and our perspectives for future development in structural biomaterials.