Compartmentalized processing of catechols during mussel byssus fabrication determines the destiny of DOPA

Significance Catechol chemistry has emerged as a cornerstone of bioinspired polymers and adhesives due to its versatility in creating diverse covalent and dynamic noncovalent interactions (including metal coordination). The concept initially arose from the discovery that mussels use catechol moieties of 3,4-dihydroxyphenylalanine (DOPA) to mediate robust surface adhesion in seawater and to reinforce tough and self-healing biopolymer fibers. Currently, difficulties controlling DOPA redox chemistry limit its synthetic application; yet, mussels overcome this challenge daily through apparent physical and chemical process control. Here, we reveal that mussels employ several different processing pathways that predetermine the cross-linking fate of DOPA-containing proteins via spatiotemporal control of microenvironments in secretory vesicles and later in mature threads—with key significance for advanced polymer design.