Globular proteins as functional-mechanical materials: a multiscale perspective on design, processing, and applications

Globular proteins, traditionally regarded as non-structural biomolecules due to the limited load-bearing capacity in their monomeric states, are increasingly recognized as valuable building blocks for functional-mechanical materials. Their inherent bioactivity, chemical versatility, and structural tunability enable the design of materials that combine biological functionality with tailored mechanical performance. This review highlights recent advances in engineering globular proteins-spanning natural systems (serum albumins, enzymes, milk globulins, silk sericin, and soy protein isolates) to recombinant architectures including tandem-repeat proteins-into functional-mechanical platforms. We discuss strategies such as sequence engineering, crosslinking chemistry, hybrid modulation, and hierarchical assembly to enhance the mechanical properties. Diverse material formats including fibers, films, hydrogels, and porous scaffolds are examined, along with processing techniques like wet/electro-spinning, 3D printing, and self-assembly suited to the proteins' thermal and solubility constraints. Emerging applications span tissue engineering, soft electronics, and environmentally adaptive systems. Key challenges such as maintaining functional activity during reinforcement, achieving interfacial stability, and developing scalable, standardized processing methods are critically evaluated. By repositioning globular proteins as dynamic, tunable material platforms, this work aims to inspire new directions in the development of intelligent, biocompatible, and sustainable materials.