Engineered Protein Fibers with Reinforced Mechanical Properties Via β‐Sheet High‐Order Assembly

Abstract Protein fibers are ideal alternatives to synthetic polymers due to their unique mechanical properties, biocompatibility, and sustainability. However, engineering biomimetic protein fibers with high mechanical properties remains challenging, particularly in mimicking the high molecular weight of natural proteins and regulating their complex hierarchical structures. Here, a modular design and multi‐scale assembly strategy is developed to manufacture robust protein fibers using low‐ or medium‐molecular‐weight proteins. The distinct functional and structural properties of flexible, rigid, and cross‐linked domains in modular proteins are skillfully harnessed. By regulating the ratio of rigid to flexible domains, the formation of high‐order β‐sheet crystals aligned along the fiber axis is promoted, enhancing both strength and toughness. Furthermore, the dynamic imine cross‐linking network, formed by the aldehyde‐amine condensation reaction of the cross‐linked domains, further reinforces the protein fibers. Remarkably, fibers spun from modular proteins significantly smaller than natural spidroin exhibit outstanding mechanical properties, surpassing those of protein fibers with same or even higher molecular weights. This strategy offers a promising pathway for fabricating protein fibers suitable for diverse applications.