Nature has endowed us with some complex enzymes capable of utilizing proteins as their substrates to generate functional proteins through post-translational modification. However, nanozymes’ interplay with proteins as substrates is scarce, with their chemistry predominantly established using only small molecule substrates, featuring a significant gap in this area. Due to the huge prospects of nanozymes in biotechnological and therapeutic interventions, studies establishing the unexplored roles of nanozymes in the biological environments and their interplay beyond small molecule substrates warrant immediate attention. In this study, we unveil the unprecedented role of a Mn-based oxidase nanozyme (MnN) in activating a structural protein, collagen, and covalently crosslinking its tyrosine residues with only a trace amount of tannic acid (TA) without compromising its triple-helical structural integrity. While therapeutic applications demand materials prepared from collagen, the current chemical and physical crosslinking of collagen often presents significant challenges such as toxicity, denaturation, or high costs. MnN lucidly accomplishes crosslinking interplay at its 101 facets using oxygen as a co-substrate under mild conditions. This process takes advantage of MnN being active at mild acidic pH where collagen preferentially exists as a soluble triple helix (monomeric form), exposing functionalities and enhancing the crosslinking degree. Importantly, this reaction also confers 100% resistance to collagenase attack on the collagen tendon-derived biological material. The catalyzed TA–tyrosine linkage in the telopeptide region of collagen probably impedes the initial recognition step of collagenase, providing robust protection against its degradative action. Our study not only expands the repertoire of nanozymes’ substrates beyond the existing library of small molecules but also establishes a significant step toward designing a gold standard for collagen crosslinking. With biomedical applications demanding biomaterials derived from protein scaffolds with preserved structural integrity, our investigation bridges the gap between nanozymes’ chemistry and crosslinking proteins, opening exciting prospects for biomaterial development.
This article is Open Access
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