Marine Collagens Dario Fassini, Iain C

pubs.acs.org/Biomac Review Diverse and Productive Source of Biopolymer Inspiration: Marine Collagens Dario Fassini, Iain C. Wilkie, Marina Pozzolini, Cinzia Ferrario, Michela Sugni, Miguel S. Rocha, Marco Giovine, Francesco Bonasoro, Tiago H. Silva,* and Rui L. Reis Cite This: https://doi.org/10.1021/acs.biomac.1c00013 Read Online ACCESS Metrics & More Article Recommendations ABSTRACT: Marine biodiversity is expressed through the huge variety of vertebrate and invertebrate species inhabiting intertidal to deep-sea environments. The extraordinary variety of “forms and functions” exhibited by marine animals suggests they are a promising source of bioactive molecules and provides potential inspiration for different biomimetic approaches. This diversity is familiar to biologists and has led to intensive investigation of metabolites, polysaccharides, and other compounds. However, marine collagens are less well-known. This review will provide detailed insight into the diversity of collagens present in marine species in terms of their genetics, structure, properties, and physiology. In the last part of the review the focus will be on the most common marine collagen sources and on the latest advances in the development of innovative materials exploiting, or inspired by, marine collagens. 1. INTRODUCTION marine collagens have dealt with those derived from vertebrates, whereas invertebrates have been quite neglected According to recent estimates there are 7.7 million animal as a source of these molecules. species on the Earth; of these, around 2.1 million inhabit This review will give an overview of the general character- marine environments.1 Although there is no doubt that istics of collagens before examining the main sources of marine terrestrial ecosystems are both richer and better known in collagens, the main applications for these collagens, and the terms of numbers of species, the scenario is reversed when 1,2 main challenges and future opportunities that might be higher taxonomic levels are taken into account, possibly due encountered during a deeper exploration of marine collagens. to the greater stability of the aquatic environments during their evolutionary histories. This is also demonstrated by the wide 2. COLLAGEN FUNDAMENTALS Downloaded via UNIVERSIDADE DO MINHO 01000 on April 13, 2021 at 11:47:37 (UTC). variety of morphologies and physiologies shown by aquatic See https://pubs.acs.org/sharingguidelines for options on how to legitimately share published articles. species and by the wide range of metabolites that are a valuable Collagens are a large family of proteins that form the main source of bioactive compounds with biomedical applica- organic portion of the extracellular matrix (ECM). Collagens, 3−5 with the possible exceptions represented by Placozoa9 and tions. 10 11 Animals appeared and mostly evolved in water; one of the Rotifera, are often considered to be a metazoan hallmark, and their appearance led to the creation of an extracellular key factors that led to the passage from small cell aggregates to ff a variety of large animals is thought to be the appearance of a sca olding that allowed the transition from microscopic relatively simple but highly hierarchical protein: collagen.6,7 protozoans to the macroscopic multicellular complexity of metazoans.6 Collagens are highly hierarchical proteins, and by Besides being a key molecule in the life histories and evolution fi fi of more complex life forms, collagen also represents a valuable forming brils, micro brillar networks, and basement mem- branes, they represent the most abundant proteins in many compound for different biotechnological fields. Collagens, in particular marine collagens, have recently attracted the attention of scientists, as demonstrated by the Received: January 6, 2021 increasing number of publications in the last 15 years.8 Marine Revised: March 26, 2021 collagens and collagen-derived products, such as gelatin and collagen peptides, have shown interesting properties in comparison with the more traditional and established sources (mainly bovine and porcine). Most of the investigations of © XXXX American Chemical Society https://doi.org/10.1021/acs.biomac.1c00013 A Biomacromolecules XXXX, XXX, XXX−XXX Biomacromolecules pubs.acs.org/Biomac Review animals and the main building blocks of most connective where, depending on the collagen type, the N- and C- tissues and organs. propeptides can be removed by procollagen N- and Collagen is particularly abundant in connective tissues where procollagen C-proteinase.21 Once in the ECM, collagens its main functions are to transmit, resist, and dissipate undergo a spontaneous process of high-order alignment that is mechanical forces and to store and release elastic strain characteristic for each collagen subfamily (structural organ- energy.12 As well as forming well-organized structures that ization is detailed in section 2.2). contribute to the cellular scaffolding and confer mechanical After collagens have been released and have acquired their stability on tissues and organs, collagens also present specific conformation in the ECM, they undergo a set of modifications. binding domains that have many important functions in The nature of these modifications depends largely on the different physiological processes. Through the presence of degree of quantitative and qualitative post-translational molecule-binding motifs, collagens are involved in the storage modifications, the tissue where they are secreted, and the age and release of cellular mediators, thus playing a critical role of the individual (see ref 22 for an extensive review of collagen during development and during the repair and regeneration of maturation and modifications). The modifications can be 13−16 tissues and organs. One well-known binding site is the divided roughly into two different categories: those that cross- 17 RGD motif, which binds fibronectin. link procollagen with divalent bonds and those that modify 11 So far almost 30 types of collagen have been described. All mature collagen via trivalent cross-links and glycation. of them have repeated Gly-Xaa-Yaa tripeptide sequences The end-overlap quarter-staggered alignment, typical of (where Xaa and Yaa are most commonly proline and fibril-forming collagen types I and III, is promoted by the hydroxyproline, respectively, but can be any amino acid), specific divalent cross-linking of residues in the telopeptides which are mainly responsible for the presence of the α helix 8 (9N and 16C) and in the helical region (residues 87 and 930). domain. In the helical region the sites involved have the specific amino 2.1. Collagen Synthesis. As is the case with all proteins, acid sequence Hyl-Gly-His-Arg-Gly.22 The aldehyde groups collagen synthesis starts with DNA transcription following formed in the telopeptide sites can react with the hydroxylysine fi speci c signals (Figure 1). in this sequence of the helix due to the staggering of the molecules, thus contributing to the stabilization of the structure. In the network-forming collagen type IV, the sequence is slightly different, with the His being substituted by Glu;22 here, the cross-links occur at the 7S N-terminal region of adjacent molecules, while cross-linking between two consecutive type IV collagen molecules is provided by stable disulfide bonds.23 The process of collagen maturation also involves further intra-/intermolecular cross-linking and is responsible for the increasing insolubility and mechanical strength of older collagenous tissues. The process depends on several different reactions between amino acidic groups as well as on glycation processes that have important consequences for collagen structure and properties (see ref 22 for an extensive and detailed review). 2.2. Collagen Types and Microstructures. As discussed above, all collagens are characterized by the presence of a Figure 1. Graphical representation of the collagen synthesis and specific region where three polypeptide chains self-assemble to secretion pathway. GT, hydroxylysyl galactosyltransferase/galactosyl- form a tightly bonded triple helix structure. The presence of hydroxylysyl glucosyltransferase; LH, lysin hydroxylase; HSP 47, heat these regions is due to the strong tendency for proline-rich shock protein 47; OTC, oligosaccharyl transferase complex; PDI, repeated Gly-Xaa-Yaa tripeptide sequences to assume this protein disulfide isomerase; PH, proline hydroxylase; PPI, peptidyl- − conformation (see for instance ref 24 for a detailed explanation prolyl cis trans-isomerase; R, ribosome. Adapted from Advanced of the chemical bonds involved). Drug Delivery Reviews, 55 (12), Gelse, K., Pöschl, E., Aigner, T., fi ff Collagens - Structure, Function, and Biosynthesis, 1531−1546, Collagens can be classi ed according to the di erent Copyright 2003, with permission from Elsevier. supramolecular aggregations formed by the aforementioned triple helices. According to Bailey and co-workers22 collagen fi After gene translation and eventual alternative splicing assembly results in the formation of bril-forming collagens, events, the peptide sequences are produced by the ribosomes fibril-associated collagens with interrupted triple helices and processed by the RER/Golgi where post-transcriptional (FACIT), network-forming collagens, anchoring fibrils, trans- modifications take place. Gene translation and alternative membrane collagens, basement membrane collagens, and splicing depend largely on cell phenotype and physiological others with unique functions (see also ref 24). state: different cytokines

Load more