Proteins for Hyperelastic Materials

Abstract Meticulous engineering and the yielded hyperelastic performance of structural proteins represent a new frontier in developing next‐generation functional biomaterials. These materials exhibit outstanding and programmable mechanical properties, including elasticity, resilience, toughness, and active biological characteristics, such as degradability and tissue repairability, compared with their chemically synthetic counterparts. However, there are several critical issues regarding the preparation approaches of hyperelastic protein‐based materials: limited natural sequence modules, non‐hierarchical assembly, and imbalance between compressive and tensile elasticity, leading to unmet demands. Therefore, it is pivotal to develop an alternative strategy for biofabricating hyperelastic materials. Herein, the molecular design, engineering, and property regulation of hyperelastic structural proteins are overviewed. First, methodologies for deeper exploration of mechanical modules, including machine learning‐aided de novo design, random mutations of natural sequences, and multiblock fusion techniques, are actively introduced. These methodologies facilitate the generation of elastomeric protein modules and demonstrate enhanced structural and functional versatility. Subsequently, assembly tactics of hyperelastic proteins (i.e., physical modulation, genetic adaptations, and chemical modifications) are reviewed, yielding hierarchically ordered structures. Finally, advances in biophysical techniques for more nuanced characterization of protein ensembles are discussed, unveiling the tuning mechanisms of protein elasticity across scales. Future developments in structural hyperelastic protein‐based biomaterials are also envisioned.