Essential Role of Thiols in Maintaining Stable Catecholato-Iron Complexes in Condensed Materials

The load-bearing proteins in mussel holdfasts rely on condensed tris-catecholato-Fe3+ coordination complexes for their toughness and shock-absorbing properties, and this feature has been successfully translated into synthetic materials with short-term high-performance properties. However, oxidation of catecholic DOPA (3,4-dihydroxyphenylalanine) remains a critical impediment to achieving materials with longer-lasting performance. Here, following the natural mussel pathway for protein processing, we explore how DOPA oxidation impacts coacervation of mussel foot protein-1 (mfp-1) and its capacity for phase-specific metal uptake in vitro. Without metal, DOPA oxidation changed the rheological properties (i.e., viscosity, loss, and storage moduli) of mfp-1 coacervate droplets. However, oxidation-dependent changes were recovered with dithiothreitol (DTT), completely restoring the behavior of mfp-1 coacervates prior to oxidation. With metal, mfp-1 coacervates exhibited gel-like behavior with high viscosity and cohesive forces by forming recognizable bis- and tris-catecholato-Fe complexes, linked to increased energy dissipation and toughness of byssus. These results indicate that Fe3+-mediated conversion of liquid–liquid phase-separated polymers into metal-coordinated networks is thorough and rapid, and DTT effectively maintains redox integrity. Our study provides much-needed improvements for processing catechol-functionalized polymers into high-performance materials.