Mutable collagenous tissue: A concept generator for biomimetic materials and devices

Echinoderms (starfish, sea-urchins and their close relations) possess a unique type of collagenous tissue that is innervated by the motor nervous system and whose mechanical properties, such as tensile strength and elastic stiffness, can be altered in a time frame of seconds. Intensive research on echinoderm ‘mutable collagenous tissue’ (MCT) began over 50 years ago, and over 20 years ago, MCT first inspired a biomimetic design. MCT, and sea-cucumber dermis in particular, is now a major source of ideas for the development of new mechanically adaptable materials and devices with applications in diverse areas including biomedical science, chemical engineering and robotics. In this review, after an up-to-date account of present knowledge of the structural, physiological and molecular adaptations of MCT and the mechanisms responsible for its variable tensile properties, we focus on MCT as a concept generator surveying biomimetic systems inspired by MCT biology, showing that these include both bio-derived developments (same function, analogous operating principles) and technology-derived developments (same function, different operating principles), and suggest a strategy for the further exploitation of this promising biological resource

Gli echinodermi come modelli per lo studio di Distruttori Endocrini: un approccio integrato

Gli echinodermi rappresentano dei validi modelli sperimentali nell\u2019ambito dell\u2019ecotossicologia marina. Essi infatti sono organismi bentonici a diretto contatto con potenziali fonti di xenobiotici e offrono un ampio range di processi biologici utili per questo tipo di approccio. In questo lavoro sono presentati i risultati pi\uf9 significativi ottenuti nel nostro laboratorio utilizzando questi organismi come modelli per lo studio degli effetti di potenziali Distruttori Endocrini (ED). Sono stati presi in esame due diverse specie di echinodermi, il riccio di mare Paracentrotus lividus e il crinoide Antedon mediterranea, e due diversi aspetti della loro fisiologia, la biologia riproduttiva e lo sviluppo rigenerativo, rispettivamente. Esemplari adulti di entrambe le specie sono stati esposti a diversi ED, potenzialmente in grado di interferire con gli ormoni sessuali. Le concentrazioni utilizzate erano comparabili a quelle ambientali. La ricerca si \ue8 basata su un approccio multidisciplinare che ha previsto analisi morfologiche, chimiche e biochimiche. I risultati ottenuti hanno evidenziato la capacit\ue0 di questi composti di interferire con diversi parametri quali la crescita rigenerativa, il pattern istologico e il diametro delle uova prodotte, sebbene lo specifico meccanismo d\u2019azione sia ancora da chiarire. Infatti, nel caso di P. lividus, la somministrazione diretta di ormoni sessuali, quali l\u2019estradiolo, non produce effetti significativi sulla biologia riproduttiva dell\u2019animale. Nel complesso i risultati ottenuti sottolineano sia l\u2019importanza di utilizzare modelli alternativi nei test ecotossicologici sia la necessit\ue0 di approfondire maggiormente la fisiologia di base degli organismi modello

Ultrastructural and biochemical characterization of mechanically adaptable collagenous structures in the edible sea urchin Paracentrotus lividus

The viscoelastic properties of vertebrate connective tissues rarely undergo significant changes withinphysiological timescales, the only major exception being the reversible destiffening of the mammalianuterine cervix at the end of pregnancy. In contrast to this, the connective tissues of echinoderms (seaurchins, starfish, sea cucumbers, etc.) can switch reversibly between stiff and compliant conditions intimescales of around a second to minutes. Elucidation of the molecular mechanism underlying suchmutability has implications for the zoological, ecological and evolutionary field. Important informationcould also arise for veterinary and biomedical sciences, particularly regarding the pathological plasti-cization or stiffening of connective tissue structures. In the present investigation we analyzed aspectsof the ultrastructure and biochemistry in two representative models, the compass depressor ligamentand the peristomial membrane of the edible sea urchin Paracentrotus lividus, compared in three differentmechanical states. The results provide further evidence that the mechanical adaptability of echinodermconnective tissues does not necessarily imply changes in the collagen fibrils themselves. The higher gly-cosaminoglycan (GAG) content registered in the peristomial membrane with respect to the compassdepressor ligament suggests a diverse role of these molecules in the two mutable collagenous tissues.The possible involvement of GAG in the mutability phenomenon will need further clarification. Duringthe shift from a compliant to a standard condition, significant changes in GAG content were detected onlyin the compass depressor ligament. Similarities in terms of ultrastructure (collagen fibrillar assembling)and biochemistry (two alpha chains) were found between the two models and mammalian collagen.Nevertheless, differences in collagen immunoreactivity, alpha chain migration on SDS-PAGE and BLASTalignment highlighted the uniqueness of sea urchin collagen with respect to mammalian collagen

Echinoderms are valid deuterostome marine invertebrate models to study repair phase events after arm injury

Echinoderms are often subjected to traumatic amputations that damage or remove whole body parts i.e. arms. After such severe injuries, the repair phase must be effective with rapid emergency reaction and re-epithelialisation as well finely regulated extracellular matrix (ECM) remodelling to ensure subsequent arm regeneration. Here, we used the brittle star Amphiura filiformis (Ophiuroidea) and the starfish Echinaster sepositus (Asteroidea) as valid deuterostome marine invertebrate models to study similarities and differences in the repair phase phenomena of these two echinoderm species and discuss them in comparison with those of animals with limited regenerative abilities (i.e. mammals). To achieve this goal, we used an integrated approach based on both microscopy and molecular analyses. We showed that in both echinoderm models, immediately after injury, emergency reaction and re-epithelialisation are extremely rapid and more efficient than those displayed by mammals. The remodelling and the formation of the ECM, mainly collagen, is ensured by delayed activation of ECM genes and protein deposition and, together with absence of fibrosis (i.e. over-deposition of ECM), seem to be advantageous for regeneration-competent animals in comparison to mammals. Overall, we found that the echinoderm species here studied show comparable repair events. The differences between regeneration-competent and non-competent animals suggest that rapid wound closure and delayed ECM deposition are necessary to ensure an effective regeneration of whole lost body parts. Further molecular and functional analyses must be performed to confirm this hypothesis

Inhibition of cell proliferation does not slow down echinoderm neural regeneration

BACKGROUND: Regeneration of the damaged central nervous system is one of the most interesting post-embryonic developmental phenomena. Two distinct cellular events have been implicated in supplying regenerative neurogenesis with cellular material – generation of new cells through cell proliferation and recruitment of already existing cells through cell migration. The relative contribution and importance of these two mechanisms is often unknown. METHODS: Here, we use the regenerating radial nerve cord (RNC) of the echinoderm Holothuria glaberrima as a model of extensive post-traumatic neurogenesis in the deuterostome central nervous system. To uncouple the effects of cell proliferation from those of cell migration, we treated regenerating animals with aphidicolin, a specific inhibitor of S-phase DNA replication. To monitor the effect of aphidicolin on DNA synthesis, we used BrdU immunocytochemistry. The specific radial glial marker ERG1 was used to label the regenerating RNC. Cell migration was tracked with vital staining with the lipophilic dye DiI. RESULTS: Aphidicolin treatment resulted in a significant 2.1-fold decrease in cell proliferation. In spite of this, the regenerating RNC in the treated animals did not differ in histological architecture, size and cell number from its counterpart in the control vehicle-treated animals. DiI labeling showed extensive cell migration in the RNC. Some cells migrated from as far as 2 mm away from the injury plane to contribute to the neural outgrowth. CONCLUSIONS: We suggest that inhibition of cell division in the regenerating RNC of H. glaberrima is compensated for by recruitment of cells, which migrate into the RNC outgrowth from deeper regions of the neuroepithelium. Neural regeneration in echinoderms is thus a highly regulative developmental phenomenon, in which the size of the cell pool can be controlled either by cell proliferation or cell migration, and the latter can neutralize perturbations in the former. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12983-017-0196-y) contains supplementary material, which is available to authorized users

Matrix metalloproteinases in a sea urchin ligament with adaptable mechanical properties

Mutable collagenous tissues (MCTs) of echinoderms show reversible changes in tensile properties (mutability) that are initiated and modulated by the nervous system via the activities of cells known as juxtaligamental cells. The molecular mechanism underpinning this mechanical adaptability has still to be elucidated. Adaptable connective tissues are also present in mammals, most notably in the uterine cervix, in which changes in stiffness result partly from changes in the balance between matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). There have been no attempts to assess the potential involvement of MMPs in the echinoderm mutability phenomenon, apart from studies dealing with a process whose relationship to the latter is uncertain. In this investigation we used the compass depressor ligaments (CDLs) of the sea-urchin Paracentrotus lividus. The effect of a synthetic MMP inhibitor - galardin - on the biomechanical properties of CDLs in different mechanical states ("standard", "compliant" and "stiff") was evaluated by dynamic mechanical analysis, and the presence of MMPs in normal and galardin-treated CDLs was determined semi-quantitatively by gelatin zymography. Galardin reversibly increased the stiffness and storage modulus of CDLs in all three states, although its effect was significantly lower in stiff than in standard or compliant CDLs. Gelatin zymography revealed a progressive increase in total gelatinolytic activity between the compliant, standard and stiff states, which was possibly due primarily to higher molecular weight components resulting from the inhibition and degradation of MMPs. Galardin caused no change in the gelatinolytic activity of stiff CDLs, a pronounced and statistically significant reduction in that of standard CDLs, and a pronounced, but not statistically significant, reduction in that of compliant CDLs. Our results provide evidence that MMPs may contribute to the variable tensility of the CDLs, in the light of which we provide an updated hypothesis for the regulatory mechanism controlling MCT mutability

Mechanical properties of the compass depressors of the sea-urchin Paracentrotus lividus (Echinodermata, Echinoidea) and the effects of enzymes, neurotransmitters and synthetic tensilin-like protein

The compass depressors (CDs) of the sea-urchin lantern are ligaments consisting mainly of discontinuous collagen fibrils associated with a small population of myocytes. They are mutable collagenous structures, which can change their mechanical properties rapidly and reversibly under nervous control. The aims of this investigation were to characterise the baseline (i.e. unmanipulated) static mechanical properties of the CDs of Paracentrotus lividus by means of creep tests and incremental force-extension tests, and to determine the effects on their mechanical behaviour of a range of agents. Under constant load the CDs exhibited a three-phase creep curve, the mean coefficient of viscosity being 561±365 MPa.s. The stress-strain curve showed toe, linear and yield regions; the mean strain at the toe-linear inflection was 0.86±0.61; the mean Young's modulus was 18.62±10.30 MPa; and the mean tensile strength was 8.14±5.73 MPa. Hyaluronidase from Streptomyces hyalurolyticus had no effect on creep behaviour, whilst chondroitinase ABC prolonged primary creep but had no effect on secondary creep or on any force-extension parameters; it thus appears that neither hyaluronic acid nor sulphated glycosaminoglycans have an interfibrillar load transfer function in the CD. Acetylcholine, the muscarinic agonists arecoline and methacholine, and the nicotinic agonists nicotine and 1-[1-(3,4-dimethyl-phenyl)-ethyl]-piperazine produced an abrupt increase in CD viscosity; the CDs were not differentially sensitive to muscarinic or nicotinic agonists. CDs showed either no, or no consistent, response to adrenaline, L-glutamic acid, 5-hydroxytryptamine and γ-aminobutyric acid. Synthetic echinoid tensilin-like protein had a weak and inconsistent stiffening effect, indicating that, in contrast to holothurian tensilins, the echinoid molecule may not be involved in the regulation of collagenous tissue tensility. We compare in detail the mechanical behaviour of the CD with that of mammalian tendon and highlight its potential as a model system for investigating poorly understood aspects of the ontogeny and phylogeny of vertebrate collagenous tissues.(undefined)info:eu-repo/semantics/publishedVersio