Mussel mooring made mighty by metals: Mussels produce an exceptional proteinaceous adhesive so they can withstand waves and currents. Metal ions bound to modified tyrosine residues play an important role in reinforcing the adhesive. Priemel et al . brought together a variety of spectroscopy and microscopy techniques to study the cellular mechanisms involved in adhesive fabrication in mussels (see the Perspective by Wilker). They found that metal ion–rich vesicles are secreted alongside vesicles containing the adhesive protein and mix in a microfluidic-like process within interconnected microchannels found in the lateral duct of the mussel foot to create porous, adhesive plaque filaments. —MAF

Biology offers a valuable inspiration toward the development of self-healing engineering composites and polymers. In particular, chemical level design principles extracted from proteinaceous biopolymers, especially the mussel byssus, provide inspiration for design of autonomous and intrinsic healing in synthetic polymers. The mussel byssus is an acellular tissue comprised of extremely tough protein-based fibers, produced by mussels to secure attachment on rocky surfaces. Threads exhibit self-healing response following an apparent plastic yield event, recovering initial material properties in a time-dependent fashion. Recent biochemical analysis of the structure–function relationships defining this response reveal a key role of sacrificial cross-links based on metal coordination bonds between Zn²⁺ ions and histidine amino acid residues. Inspired by this example, many research groups have developed self-healing polymeric materials based on histidine (imidazole)–metal chemistry. In this review, we provide a detailed overview of the current understanding of the self-healing mechanism in byssal threads, and an overview of the current state of the art in histidine- and imidazole-based synthetic polymers.

The mussel byssus stem provides a strong and compact mechanically mismatched biointerface between living tissue and a nonliving biopolymer. Yet, in a poorly understood process, mussels can simply jettison their entire byssus, rebuilding a new one in just hours. We characterized the structure and composition of the byssus biointerface using histology, confocal Raman mapping, phase contrast–enhanced microcomputed tomography, and advanced electron microscopy, revealing a sophisticated junction consisting of abiotic biopolymer sheets interdigitated between living extracellular matrix. The sheet surfaces are in intimate adhesive contact with billions of motile epithelial cilia that control biointerface strength and stem release through their collective movement, which is regulated neurochemically. We posit that this may involve a complex sensory pathway by which sessile mussels respond to environmental stresses to release and relocate.

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.

Complex hierarchical structure governs emergent properties in biopolymeric materials; yet, the material processing involved remains poorly understood. Here, we investigated the multi-scale structure and composition of the mussel byssus cuticle before, during and after formation to gain insight into the processing of this hard, yet extensible metal cross-linked protein composite. Our findings reveal that the granular substructure crucial to the cuticle’s function as a wear-resistant coating of an extensible polymer fiber is pre-organized in condensed liquid phase secretory vesicles. These are phase-separated into DOPA-rich proto-granules enveloped in a sulfur-rich proto-matrix which fuses during secretion, forming the sub-structure of the cuticle. Metal ions are added subsequently in a site-specific way, with iron contained in the sulfur-rich matrix and vanadium coordinated by DOPA-catechol in the granule. We posit that this hierarchical structure self-organizes via phase separation of specific amphiphilic proteins within secretory vesicles, resulting in a meso-scale structuring that governs cuticle function.