Mussel Foot Proteins: From Molecular Mechanisms to Production Strategy and Application

ConspectusAchieving strong and durable adhesion in aquatic, dynamic environments is a significant challenge. Marine mussels address this through byssal threads secured by Mussel Foot Proteins (Mfps). Comprising several main variants (Mfp-1 to Mfp-6) with distinct structures, Mfps serve as an important model in bioadhesion, providing key insights for synthetic material design. Their functionality is due to 3,4-dihydroxyphenylalanine (DOPA), which is “A significant yet not the sole chemical factor” and “one of the key sources of inspiration” within complex adhesion systems. These catechol groups of DOPA mediate a two-stage adhesion process. Initially, they facilitate rapid surface wetting and attachment through noncovalent interactions such as hydrogen bonding, cation-π interactions, and hydrophobic effects. Subsequently, oxidation can convert catechols to quinones, which enable covalent cross-linking for cohesion and stable substrate anchoring via reactions with nucleophiles or metal ion coordination. This combination of reversible and irreversible interactions underpins the robust adhesion of Mfps in marine settings.Understanding these natural mechanisms has significantly advanced adhesive technology, leading to diverse Mfp materials. Beyond mimicking natural proteins, synthetic biology and polymer chemistry have been employed to replicate and extend these principles. Recombinant expression allows the production of tailored proteins, while synthetic peptides capture core functional motifs. This approach has led to a range of functional biomaterials with applications extending beyond adhesion, including tissue adhesives, antifouling coatings, drug delivery systems, self-healing hydrogels, and biosensors.Current research is exploring more dynamic and multifunctional systems based on the Mfps principles. Future efforts may focus on environmentally responsive materials that offer spatiotemporal control over the adhesion. Integrating Mfp designs with synthetic biology could also contribute to developing engineered living materials. Key research directions include the computational design of adhesive peptides, protein engineering for stability, optimization of microbial expression systems for production, and improved purification strategies. Realizing the practical potential of Mfp-based technologies will require addressing persistent challenges in scalable production and controlling catechol oxidation through interdisciplinary efforts in molecular design, materials science, and engineering.