Molecularly Engineered Protein Glues with Superior Adhesion Performance

Abstract Naturally inspired proteins are investigated for the development of bioglues that combine adhesion performance and biocompatibility for biomedical applications. However, engineering such adhesives by rational design of the proteins at the molecular level is rarely reported. Herein, it is shown that a new generation of protein‐based glues is generated by supramolecular assembly through de novo designed structural proteins in which arginine triggers robust liquid–liquid phase separation. The encoded arginine moieties significantly strengthen multiple molecular interactions in the complex, leading to ultrastrong adhesion on various surfaces, outperforming many chemically reacted and biomimetic glues. Such adhesive materials enable quick visceral hemostasis in 10 s and outstanding tissue regeneration due to their robust adhesion, good biocompatibility, and superior antibacterial capacity. Remarkably, their minimum inhibitory concentrations are orders of magnitude lower than clinical antibiotics. These advances offer insights into molecular engineering of de novo designed protein glues and outline a general strategy to fabricate mechanically strong protein‐based materials for surgical applications.