# Routes towards Novel Collagen-Like Biomaterials
## 3 Mussel Byssus-Silk, Collagen or Both? Among the byssus-producing mussels, the blue mussel, _Mytilus edulis_ and the closely related mediterranean mussel _Mytilus galloprovincialis_ are the best characterized. These species produce a bundle of threads which connects the soft mussel to the substrate, and the threads show a mechanical gradient with increasing stiffness from the proximal to the distal portion of the fiber. This allows the byssus to dissipate high amounts of mechanical energy without causing radial stress between the parts with highly different elastic moduli, thereby withstanding the mechanical challenges caused by the tidal currents without damaging the soft mollusk's organs and tissues. The byssus thread itself is rather complex and contains a large set of matrix proteins, called mussel foot proteins (mfp's), which, in addition to contributing to the chemical and physical properties of the fibrous portion of the thread, form an adhesive plaque that is just as remarkable as the rest of the byssus, since it provides strong and durable underwater adhesion to a variety of substrates with different chemical compositions. These somewhat amorphous matrix proteins interact with the main load bearing structure of the byssus, which are called preCols because of their collagen-like structure. The three known preCols of _M. edulis_ are block-copolymers which consist of a central collagen-like core domain that is surrounded by flanking domains [80]. Even though the preCols differ strongly from vertebrate collagens in that they are homotrimers and do not undergo the same kind of propeptide processing, their central collagen-like core domain has been described to be most closely related to that of fibrillar collagens (type I-III) [81]. It has to be noted, however, that most of the mechanical properties of the preCols are attributed to the flanking domains, which make up a significant portion of every preCol [14; 81; 82]. Depending on the type of preCol, these flanking domains contain motifs that are similar to other structural proteins: preColD contains silk-fibroin-like flanks, the flanks of preColP shows similarity to elastin and preColNG contains plant cell wall-like sequences, which include features of alanine-rich \(\beta\)-sheets as well as glycine-rich helices (Figure 3a,b). While the macroscopic byssus threads of _M. edulis_ and _M. galloprovincialis_ differ slightly in size and in their mechanical properties, the preCols are closely related on a molecular level and only differ in short inserts/deletions and point mutations [83]. In addition to the flanking domains, the preCols all contain terminal domains which are rich in histidine and 3,4-dihydroxyphenylalanine (DOPA, post-translationally oxidized tyrosine) which form sacrificial metal ion mediated complexes that can absorb mechanical stress and reassemble over time without taking damage [84]. In addition, they undergo a slow quinone-based tanning, thereby forming irreversible crosslinks with other proteins in the byssus and providing a redox-dependent mechanism further stabilizing the byssus [85; 86]. One remarkable observation is the fact that the previously mentioned mechanical gradient corresponds to the abundance of preColP and preColD within the respective section of the byssus thread. The proximal section of the byssus, which connects to the stem within the mussel and has a Young's modulus of around 50-80 MPa, is rich in preColP; while the distal portion with a stiffness of \(E_{i}\) = 500-600 MPa contains high amounts of preColD [83]. The third mussel byssus collagen, preColNG, has a constant concentration throughout the thread (Figure 4).