Search

Bioadhesives are popular characterization targets for informing the design of synthetic materials. Many naturally occurring adhesive proteins are phosphorylated, yet we do not know why phosphorylation might be so prevalent in nature. Here phosphate-containing biomimetic polymers were made using the chemistry of catechol, or 3,4-dihydroxyphenylalanine (DOPA), for adhesion. Structure-function studies were carried out with this family of poly(catechol-phosphate) polymers to determine how phosphate groups influence bulk adhesion. Bonding was studied both dry and underwater. Under some conditions polymers containing phosphate groups exhibited extreme levels of surface wetting on steel substrates. Dry adhesion increased moderately with greater phosphate content in the polymers. Underwater bonding was weaker than dry and achieved, only to a limited degree, when the polymer phosphate content was high. These results indicate that phosphates may provide an aid to the more impactful adhesive properties of catechols. Such insights may also help to explain the existence of phosphates in bioadhesives as well as inform the future design of high performance materials.

Mussel foot proteins (Mfps) secreted in the byssal plaque of marine mussels are widely researched for their relevance to mussel adhesion in water. As the abundant residue in the amino acid sequences of major adhesive proteins, 3,4-dihydroxyphenylalanine (Dopa) or its catecholic moiety plays a key role in both Mfp binding to surface and cohesive cross-linking of Mfps in byssal plaques. The binding performance of an Mfp significantly depends on the content and redox state of Dopa, whereas the types of interaction vary in line with different surface chemistries and pH conditions. Thorough understanding of mussel adhesion from a molecular perspective is crucial to promote the application of synthetic mussel-bionic adhesives. This article presents a brief review of the research progress on the adhesion mechanisms of Mfps, which further emphasizes the contributions of Dopa-mediated interactions and considers other amino acids and factors. The involved inter- and intramolecular interactions are responsible for not only the diverse adhesion capacities of an adhesive byssal plaque as mussel’s adhesion precursor but also the formation and properties of the plaque structure.

Different chemistries have been utilized for adhesive materials to achieve adhesion in a humidified environment. l-3,4-dihydroxyphenylalanine (DOPA) found in marine mussel adhesive proteins has generated great interest because DOPA participates in multiple reaction mechanisms that confer the ability to adhere in wet conditions. However, the mussel adhesive complex also contains proteins with a relatively high thiol content, and these proteins can contribute to adhesion through the formation of disulfide bonds or interactions with DOPA. This work probes the individual contributions and interactions of DOPA and thiol chemistries to adhesion. To do so, we took advantage of the sequence flexibility in elastin-like polypeptides (ELPs) to create model proteins with highly similar sequences that are rich in either DOPA or thiol residues. The sequence similarity between the two ELP adhesives allowed us to focus on the differences between DOPA- and thiol-based adhesion. Curing kinetics in a wet setting, capability to recover from disturbance in the curing process, and cytocompatibility of the two adhesives were compared. Both chemistries resulted in cytocompatible materials. However, thiol chemistry had faster curing kinetics and higher adhesion strengths, whereas DOPA chemistry showed better recovery from disturbances during the curing process. By utilizing both DOPA- and thiol-based chemistry simultaneously and adding iron ions, we achieved fast curing kinetics, strong adhesion strengths, and good recovery from disturbances to curing. These insights into the contribution of these chemistries to adhesion provide important lessons for researchers designing adhesives that work in a humid environment.

Limpets (Patella vulgata L.) are renowned for their powerful attachments to rocks on wave-swept seashores. Unlike adult barnacles and mussels, limpets do not adhere permanently; instead, they repeatedly transition between long-term adhesion and locomotive adhesion depending on the tide. Recent studies on the adhesive secretions (bio-adhesives) of marine invertebrates have expanded our knowledge on the composition and function of temporary and permanent bio-adhesives. In comparison, our understanding of the limpets' transitory adhesion remains limited. In this study, we demonstrate that suction is not the primary attachment mechanism in P. vulgata; rather, they secrete specialized pedal mucus for glue-like adhesion. Through combined transcriptomics and proteomics, we identified 171 protein sequences from the pedal mucus. Several of these proteins contain conserved domains found in temporary bio-adhesives from sea stars, sea urchins, marine flatworms and sea anemones. Many of these proteins share homology with fibrous gel-forming glycoproteins, including fibrillin, hemolectin and SCO-spondin. Moreover, proteins with potential protein- and glycan-degrading domains could have an immune defence role or assist degrading adhesive mucus to facilitate the transition from stationary to locomotive states. We also discovered glycosylation patterns unique to the pedal mucus, indicating that specific sugars may be involved in transitory adhesion. Our findings elucidate the mechanisms underlying P. vulgata adhesion and provide opportunities for future studies on bio-adhesives that form strong attachments and resist degradation until necessary for locomotion.

Cancer is one of the leading causes of death in human beings. Therefore, it is important to detect specific target tumors earlier enough in the formative stages of cancer without causing negative side effects and damages to the body. In this study, we proposed bio-engineered short mussel adhesive proteins (MAPs)-carbon nanotubes (CNTs) as specific tumor-targeted carriers for biomedical imaging. Short CNT near-infrared fluorophore (NIRF) hybrid carriers that were developed accumulated in the tumors with exceptional clearance and specific targeting in less time, and these results indicated that bioengineered short CNT-based carriers have great potential for real time tumor imaging.

Marine mussels are able to firmly affix on various wet surfaces by the overproduction of special mussel foot proteins (mfps). Abundant fundamental studies have been conducted to understand the molecular basis of mussel adhesion, where the catecholic amino acid, l-3,4-dihydroxyphenylalanine (DOPA) has been found to play the major role. These studies continue to inspire the engineering of novel adhesives and coatings with improved underwater performances. Despite the fact that the recent advances of adhesives and coatings inspired by mussel adhesive proteins have been intensively reviewed in literature, the fundamental biochemical and biophysical studies on the origin of the strong and versatile wet adhesion have not been fully covered. In this review, we show how the force measurements at the molecular level by surface force apparatus (SFA) and single molecule atomic force microscopy (AFM) can be used to reveal the direct link between DOPA and the wet adhesion strength of mussel proteins. We highlight a few important technical details that are critical to the successful experimental design. We also summarize many new insights going beyond DOPA adhesion, such as the surface environment and protein sequence dependent synergistic and cooperative binding. We also provide a perspective on a few uncharted but outstanding questions for future studies. A comprehensive understanding on mussel adhesion will be beneficial to the design of novel synthetic wet adhesives for various biomedical applications.

The capability of mediating ice nucleation is pertinent to a broad range of fields. Herein, inspired by metal-catechol coordination found in adhesive proteins in which catechol moieties can construct strong complexes with a diverse array of metal ions, we develop a platform for mediating ice nucleation based on metal-catechol complexes and demonstrate that ice nucleation can be successively mediated by varying the characteristics and valence of the metal in metal-catechol complexes.

Byssuses, which are proteinaceous fibers secreted by mollusks, are remarkable underwater adhesives. Although mussel adhesives are well known, much less is known about the byssal proteins of pearl oysters especially in the adhesive regions. In this study, adhesive proteins from the pearl oyster

Marine mussels have attracted attention in the last years due to their incredible ability to stick to various organic and inorganic substrates in harsh environments. This capacity has been attributed to specific proteins secreted by marine mussels, known as marine mussel adhesive proteins (MAPs). These proteins have in their constitution an unusual amino acid, 3,4-dihydroxyphenylalanine (DOPA). Many efforts have been made to produce materials with adhesive properties equivalent to those shown by MAPs for biomedical applications. Therefore, distinct polymeric biomaterials, either with two-dimensional or three-dimensional structures, have been developed trying to mimic this incredible adhesive performance. In this review, an overview of the application of MAPs and their adhesive properties on the development of distinct biomaterials based on both natural and synthetic polymers will be presented, namely on films and hydrogels production. The variety of biomedical applications of these bioinspired materials will be also discussed., The authors would like to acknowledge the Portuguese Foundation for Science and Technology (FCT) and the European program FEDER/ COMPETE for the financial support through projects PTDC/BTM-MAT/ 28123/2017, PTDC/NAN-MAT/31036/2017 and the exploratory project MIT-EXPL/BIO/0089/2017.

Adhesives plays an important role in industries and our daily life, mostly they are chemically processed like cyanoacrylates which are proved to be harmful for the environment thus there were many trials with various natural source. Amongst all the marine organism had the ability to adhere to surface naturally, they proved to have an adhesive part which forms a plaque or cement that allows the attachment of organisms to the sea bed. Further analysis led to the preparation of temporary, instantaneous, permanent and transitory adhesives wherein mussels and tubeworms were involved in permanent adhesion, limpets for transitory adhesion, sea stars for temporary adhesion, and sea cucumbers for instantaneous adhesion. The bonding and tensile strength of the adhesives was verified by conducting various tests to check if the adhesive improves performance. In this review we have focused on different isolation, extraction and characterization processes involved in the preparation of adhesives from marine organisms including their application in the field of medicine, engineering, biotechnology and environment.

Mussel-inspired adhesion chemistry provides a useful alternative to the use of fibrin glues., Since the first report of underwater adhesive proteins of marine mussels in 1981, numerous studies have reported mussel-inspired synthetic adhesive polymers. However, none of them have developed up to human-level translational studies. Here, we report a sticky polysaccharide that effectively promotes hemostasis from animal bleeding models to first-in-human hepatectomy. We found that the hemostatic material instantly generates a barrier layer that seals hemorrhaging sites. The barrier is created within a few seconds by in situ interactions with abundant plasma proteins. Therefore, as long as patient blood contains proper levels of plasma proteins, hemostasis should always occur even in coagulopathic conditions. To date, insufficient tools have been developed to arrest coagulopathic bleedings originated from genetic disorders, chronic diseases, or surgical settings such as organ transplantations. Mussel-inspired adhesion chemistry described here provides a useful alternative to the use of fibrin glues up to a human-level biomedical application.

Here we report the possible contribution of cation–π interaction to underwater adhesion of mussels by using DOPA-deficient recombinant mussel adhesive proteins. Considering the instability of DOPA in an oxidative environment, the cation–π interaction in DOPA-deficient biopolymers provides a complementary cross-linking mechanism for the design of novel underwater adhesives.

Available online 19 November 2019., Protein-based bioadhesives are found in diverse marine invertebrates that developed attachment devices to adhere to various substrates. These adhesives are of interest to materials science to create bioinspired-adhesives that can perform in water or wet conditions and can be applied in a broad variety of biotechnological and industrial fields. Due to the high variety of invertebrates that inhabit the marine environment, an enormous diversity of structures and principles used in biological adhesives remains unexplored and a very limited number of model systems have inspired novel biomimetic adhesives, the most notable being the mussel byssus adhesive. In this review we give an overview of other marine invertebrates studied for their bioadhesive properties in view of their interest for the development of new biomimetic adhesives for application in the biomedical field but also for antifouling coatings. The molecular features are described, highlighting relevant structures, and examples of biomimetic materials are discussed and explored, opening an avenue for a new set of medical products., The authors acknowledge the funding from the European UnionTransborder Cooperation Programme Interreg España-Portugal2014–2020 (POCTEP) under the projects 0245_IBEROS_1_E and0302_CVMAR_I_1_P and from European Union under the COST Action16203 MARISTEM.

Polydopamine is one of the simplest and most versatile approaches to functionalizing material surfaces, having been inspired by the adhesive nature of catechols and amines in mussel adhesive proteins. Since its first report in 2007, a decade of studies on polydopamine molecular structure, deposition conditions, and physicochemical properties have ensued. During this time, potential uses of polydopamine coatings have expanded in many unforeseen directions, seemingly only limited by the creativity of researchers seeking simple solutions to manipulating surface chemistry. In this review, we describe the current state of the art in polydopamine coating methods, describe efforts underway to uncover and tailor the complex structure and chemical properties of polydopamine, and identify emerging trends and needs in polydopamine research, including the use of dopamine analogs, nitrogen-free polyphenolic precursors, and improvement of coating mechanical properties.

Summary Recombinant bacterial colonization plays an indispensable role in disease prevention, alleviation, and treatment. Successful application mainly depends on whether bacteria can efficiently spatiotemporally colonize the host gut. However, a primary limitation of existing methods is the lack of precise spatiotemporal regulation, resulting in uncontrolled methods that are less effective. Herein, we design upconversion microgels (UCMs) to convert near-infrared light (NIR) into blue light to activate recombinant light-responsive bacteria (Lresb) in vivo, where autocrine “functional cellular glues” made of adhesive proteins assist Lresb inefficiently colonizing the gut. The programmable engineering platform is further developed for the controlled and effective colonization of Escherichia coli Nissle 1917 (EcN) in the gut. The colonizing bacteria effectively alleviate DSS-induced colitis in mice. We anticipate that this approach could facilitate the clinical application of engineered microbial therapeutics to accurately and effectively regulate host health.

Marine mussels exhibit potent underwater adhesion abilities under hostile conditions by employing 3,4-dihydroxyphenylalanine (DOPA)-rich mussel adhesive proteins (MAPs). However, their recombinant production is a major biotechnological challenge. Herein, a novel strategy based on genetic code expansion has been developed by engineering efficient aminoacyl-transfer RNA synthetases (aaRSs) for the photocaged noncanonical amino acid ortho-nitrobenzyl DOPA (ONB-DOPA). The engineered ONB-DOPARS enables in vivo production of MAP type 5 site-specifically equipped with multiple instances of ONB-DOPA to yield photocaged, spatiotemporally controlled underwater adhesives. Upon exposure to UV light, these proteins feature elevated wet adhesion properties. This concept offers new perspectives for the production of recombinant bioadhesives.

Photocaged DOPA derivatives may serve for non-invasive unmasking of the catechol fragment in biological systems. This would enable efficient control of the redox and metal-coordinating properties associated with the free catechol moiety, in particular, in biosynthetically produced adhesive proteins and synthetic peptides. Synthetic routes towards photocaged DOPA derivatives are reported herein. A new method for preparing para-alkylated DOPA starting from 3,4-dihydroxybenzaldehyde is described for the first time.

Barnacles are notorious marine fouling organisms, whose life cycle initiates with the planktonic larva, followed by the free-swimming cyprid that voluntarily explores, and searches for an appropriate site to settle and metamorphoses into a sessile adult. Within this life cycle, both the cyprid and the adult barnacle deposit multi-protein adhesives for temporary or permanent underwater adhesion. Here, we present a comprehensive review of the biochemistries behind these different adhesion events in the life cycle of a barnacle. First, we introduce the multiple adhesion events and their corresponding adhesives from two complementary aspects: the in vivo synthesis, storage, and secretion as well as the in vitro morphology and biochemistry. The amino acid compositions, sequences, and structures of adult barnacle adhesive proteins are specifically highlighted. Second, we discuss the molecular mechanisms of adult barnacle underwater attachment in detail by analyzing the possible adhesive and cohesive roles of different adhesive proteins, and based on these analyses, we propose an update to the original barnacle underwater adhesion molecular model. We believe that this review can greatly promote the general understanding of the molecular mechanisms underlying the reversible and irreversible underwater adhesion of barnacles and their larvae. Such an understanding is the basis for the prevention of barnacle fouling on target surfaces as well as designing conceptually new barnacle-inspired artificial underwater adhesives.

Sea stars use adhesive secretions to attach their numerous tube feet strongly and temporarily to diverse surfaces. After detachment of the tube feet, the adhesive material stays bound to the substrate as so-called ‘footprints’. In the common sea star species Asterias rubens , the adhesive material has been studied extensively and the first sea star footprint protein (Sfp1) has been characterized. We identified Sfp1-like sequences in 17 additional sea star species, representing different taxa and tube foot morphologies, and analysed the evolutionary conservation of this protein. In A. rubens , we confirmed the expression of 34 footprint proteins in the tube foot adhesive epidermis, with 22 being exclusively expressed in secretory cells of the adhesive epidermis and 12 showing an additional expression in the stem epidermis. The sequences were used for BLAST searches in seven asteroid transcriptomes providing a first insight in the conservation of footprint proteins among sea stars. Our results highlighted a high conservation of the large proteins making up the structural core of the footprints, whereas smaller, potential surface-binding proteins might be more variable among sea star species. This article is part of the theme issue ‘Transdisciplinary approaches to the study of adhesion and adhesives in biological systems’.

Many of traditional anti-corrosion approaches using chromate are effective but hazardous to natural environment and human health, so development of green and effective alternatives is desirable. One of the mussel adhesive proteins derived from mussel byssus presents extraordinary adhesion to steel surface and exhibits film-forming and corrosion inhibition properties. Novel strategies for enhancing the corrosion inhibition of steel by the protein have been demonstrated recently. The protein together with ceria nanoparticles presents a great potential for the development of new corrosion inhibitors and thin films that are ‘green’ and ‘effective’, and have ‘smart’ protection properties.

Mussel adhesive proteins (MAPs) have a unique ability to firmly adhere to different surfaces in aqueous environments via the special amino acid, 3,4-dihydroxyphenylalanine (DOPA). The catechol groups in DOPA are a key group for adhesive proteins, which is highly informative for the biomedical domain. By simulating MAPs, medical products can be developed for tissue adhesion, drug delivery, and wound healing. Hydrogel is a common formulation that is highly adaptable to numerous medical applications. Based on a discussion of the adhesion mechanism of MAPs, this paper reviews the formation and adhesion mechanism of catechol-functionalized hydrogels, types of hydrogels and main factors affecting adhesion, and medical applications of hydrogels, and future the development of catechol-functionalized hydrogels.

Hagfish defend themselves from fish predators by producing large volumes of gill-clogging slime when they are attacked. The slime consists of seawater and two major components that are ejected from the slime glands: mucus and threads. The threads are produced within specialized cells and packaged into intricately coiled bundles called skeins. Skeins are kept from unraveling via a protein adhesive that dissolves when the skeins are ejected from the slime glands. Previous work revealed that hagfish slime glands have high concentrations of methylamines including trimethylamine N-oxide (TMAO), betaine (trimethylglycine), and dimethylglycine, however the function of these compounds in the slime glands is unknown. We hypothesized that methylamines have stabilizing effects on the skeins that prevent premature unraveling in the gland. To test this hypothesis, we quantified the effect of methylamines on skein unraveling in Pacific hagfish and found that TMAO and betaine have inhibitory effects on skein unraveling in vitro. Furthermore, we found that TMAO is a more effective inhibitor of unraveling than betaine, but the presence of TMAO synergistically boosts the inhibitory action of betaine. Glycine and dimethyl glycine were far less effective inhibitors of unraveling at natural concentrations. Our results support the hypothesis that high levels of trimethylamines in the slime glands may act to hold the coiled thread skeins together within gland thread cells, and they may do so by stabilizing adhesive proteins. These results advance our knowledge of skein stabilization and deployment and provide another example of trimethylamines functioning to stabilize proteins in a marine organism.

Mussel foot adhesive proteins are one of nature's remarkable triumphs; they guarantee a secure and robust bond between the mollusc's byssal threads and the surface to which they settle ensuring that they are securely fastened. We now know that some of these adhesive proteins are especially rich in lysine and 3,4-dihydroxy-L-phenylalanine (DOPA) residues.

Inspired by the adhesive proteins of mussels, polydopamine (pDA) has emerged as one of the most widely employed methods for functionalizing material surfaces, fueled in part by the versatility, simplicity, and spontaneity of pDA film deposition on most materials upon immersion in an alkaline aqueous solution of dopamine. However, the rapid adoption of pDA for surface modification over the last decade stands in stark contrast to the slow pace in understanding the composition of pDA. Numerous attempts to elucidate the formation mechanism and structure of this fascinating material have resulted in little consensus mainly due to the insoluble nature of pDA; which renders most conventional methods of polymer molecular weight characterization ineffective.([1]) Here, we employed the non-traditional approach of single molecule force spectroscopy (SMFS) to characterize pDA films. Retraction of a pDA coated cantilever from an oxide surface shows the characteristic features of a polymer with contour lengths up to 200nm. pDA polymers are generally weakly bound to the surface through much of their contour length, with occasional “sticky” points. Our findings represent the first direct evidence for the polymeric nature of pDA and provide a foundation upon which to understand and tailor its physicochemical properties.

Although Dopa-Fe3+ complexation is known to play an important role in mussel adhesion for providing mechanical properties, its function at the plaque/substrate interface, where actual surface adhesion occurs, remains unknown, with regard to interfacial mussel adhesive proteins (MAPs) type 3 fast variant (fp-3F) and type 5 (fp-5). Here, we confirmed Dopa-Fe3+ complexation of interfacial MAPs and investigated the effects of Dopa-Fe3+ complexation regarding both surface adhesion and cohesion. The force measurements using surface forces apparatus (SFA) analysis showed that intrinsic strong surface adhesion at low pH, which is similar to the local acidified environment present during the secretion of adhesive proteins, vanishes by Dopa-Fe3+ complexation and alternatively, strong cohesion is generated in higher pH conditions similar to seawater. A high Dopa content increased the capacity for both surface adhesion and cohesion, but not at the same time. In contrast, a lack of Dopa resulted in both weak surface a...

Integrins are cell surface receptors for proteins of the extracellular matrix and plasma-borne adhesive proteins. Their involvement in diverse pathologies prompted medicinal chemists to develop small-molecule antagonists, and very often such molecules are peptidomimetics designed on the basis of the short native ligand-integrin recognition motifs. This review deals with peptidomimetic integrin ligands composed of α- and β-amino acids. The roles exerted by the β-amino acid components are discussed in terms of biological activity, bioavailability, and selectivity. Special attention is paid to the synthetic accessibility and efficiency of conformationally constrained heterocyclic scaffolds incorporating α/β-amino acid span.

Exosomes offer distinct advantages that uniquely position them as highly effective drug carriers. Comprised of cellular membranes with multiple adhesive proteins on their surface, exosomes are known to specialize in cell–cell communications and provide an exclusive approach for the delivery of various therapeutic agents to target cells. In addition, exosomes can be amended through their parental cells to express a targeting moiety on their surface, or supplemented with desired biological activity. Development and validation of exosome-based drug delivery systems are the focus of this review. Different techniques of exosome isolation, characterization, drug loading, and applications in experimental disease models and clinic are discussed. Exosome-based drug formulations may be applied to a wide variety of disorders such as cancer, various infectious, cardiovascular, and neuro-degenerative disorders. Overall, exosomes combine benefits of both synthetic nanocarriers and cell-mediated drug delivery systems while avoiding their limitations.

Cardiovascular devices have been widely applied in the clinical treatment of cardiovascular diseases. However, poor hemocompatibility and slow endothelialization on their surface still exist. Numerous surface engineering strategies have mainly sought to modify the device surface through physical, chemical, and biological approaches to improve surface hemocompatibility and endothelialization. The alteration of physical characteristics and pattern topographies brings some hopeful outcomes and plays a notable role in this respect. The chemical and biological approaches can provide potential signs of success in the endothelialization of vascular device surfaces. They usually involve therapeutic drugs, specific peptides, adhesive proteins, antibodies, growth factors and nitric oxide (NO) donors. The gene engineering can enhance the proliferation, growth, and migration of vascular cells, thus boosting the endothelialization. In this review, the surface engineering strategies are highlighted and summarized to improve hemocompatibility and rapid endothelialization on the cardiovascular devices. The potential outlook is also briefly discussed to help guide endothelialization strategies and inspire further innovations. It is hoped that this review can assist with the surface engineering of cardiovascular devices and promote future advancements in this emerging research field.

For decades, scientists have tried to make surgical glues modeled after the strong adhesive proteins that mussels use to cling to underwater surfaces. But making a practical, biocompatible glue tha...