Tyrosine-driven hierarchical self-assembly unlocks robust non-Dopa wet adsorption in marine adhesive protein.

Many marine sessile organisms achieve robust underwater adsorption through 3,4-dihydroxyphenylalanine (Dopa)-independent strategies, yet the underlying self-assembly mechanisms remain elusive. Here, we decipher the Ca2+-triggered interfacial adsorption of a sea anemone thrombospondin-1 type I repeat-like (TSRL) protein, identifying its tyrosine-rich T3 subunit as the core mediator for coating formation. The fabricated T3 coatings exhibited strong wet adsorption stability, biocompatibility, and intrinsic antioxidant activity. Mechanistically, T3 self-assembly is driven by favorable enthalpy, initiating with nanosphere aggregation and forming hierarchical fishnet-like microstructures. Molecular dynamics simulations revealed that, unlike the rapid collisions of T1 subunit, the slower diffusion of T3 enables precise orientation and pairing, leading to a marked increase in inter-residue contacts dominated by cation-π interactions between lysine and tyrosine residues, alongside π-π stacking. Mutant studies confirm that disrupting these interactions impairs both self-assembly and interfacial adsorption, establishing positioned tyrosine residues as molecular stickers. Together, these findings establish a tyrosine-mediated, non-Dopa marine adsorption paradigm and highlight the T3 protein as a promising biomaterial platform for tissue engineering and antioxidant biomedical applications. STATEMENT OF SIGNIFICANCE: This work reports a tyrosine-driven, Dopa-independent wet adsorption paradigm in marine biological systems, fundamentally expanding the current understanding of underwater adsorption mechanisms. The discovery that precisely positioned tyrosine residues can orchestrate hierarchical self-assembly through specific π-π and cation-π interactions establishes a new conceptual framework for designing bioinspired coatings. Beyond its fundamental implications, this system offers a versatile combination of robust wet adsorption and inherent biocompatibility, addressing a critical challenge in biomedical adhesive development. Moreover, the intrinsic reactive oxygen species (ROS)-scavenging capacity positions this protein-based platform as a multifunctional biomaterial with promising applications in wound healing, tissue engineering, and antioxidant therapeutics.