Berking S., Herrmann K. Formation and discharge of nematocysts is controlled by a proton gradient across the cyst membrane. . Such suited cellular test systems are fish-eggs which carry polySia on their cell surfaces. These nanomedical devices have to be effective and specific in respect to various carbohydrate signatures in the glycocalyx of tumor-cells. For a successful application of the theoretical model, it is of importance to know further details of the materials/molecules which constitute the corresponding parts in a cnidarian organism. Home / Nematocysts (Gr. The reproducible response of the system increases the entropy back to its maximum by irreversible processes: the fluctuation cannot be reproduced with a significant level of probability. The spider lectin SHL-1 [23] other small lectin-like structures have to be considered as proper polySia interacting peptides [38,39,48] on nematocyst-like nanomedical devices. Since the nematocyst discharge process is triggered by a mechanic-chemical signal which is initiated by sialic acid/polysialic acid molecules [63] on the skin of Cnidarias enemies and preys sialic acid coated nano-particles are extremely supportive artificial analytical tools beside naturally occurring sialic acid pattern on tumor cells [25,39]. Glycolipid GD3 and GD3 synthase are key drivers for glioblastoma stem cells and tumorigenicity. National Library of Medicine In the first stage of our screen for nematocyst discharge inhibitors, we used steady-state adult polyps of Hydra magnipapillata exposed to the small molecules at a concentration of 10 M in 24-well plates (see Fig. ACEP Now. Zhang R., Loers G., Schachner M., Boelens R., Wienk H., Siebert S., Eckert T., Kraan S., Rojas-Macias M.A., Ltteke T., et al. The cancer cells under study are much weaker and show a higher degree of protrusions than normal tissue cells. A comprehensive transcriptomic and proteomic analysis of Hydra head regeneration. Jayawardana K.W., Jayawardena H.S., Wijesundera S.A., De Zoysa T., Sundhoro M., Yan M. Selective targeting of Mycobacterium smegmatis with trehalose-functionalized nanoparticles. where Pthres and Y have the same dimensions, and all the lengths are scaled by the length l of the stylus. Pokidysheva E., Milbradt A.G., Meier S., Renner C., Haussinger D., Bachinger H.P., Moroder L., Grzesiek S., Holstein T.W., zbek S., et al. Haseley S.R., Vermeer H.J., Kamerling J.P., Vliegenthart J.F.G. FSNP-PFPA was synthesized by adding a solution of silane-derivatized PFPA in toluene (7.0 mL, 10 mg/mL) into the FSNP solution and stirring at room temperature for 24 h. The product was purified by repeated washing and centrifugation in acetone (12,000 rpm, 30 min), and was re-suspended in 10 mL of acetone to give FSNP-PFPA. 2012;60(4):339-414. Structures of (I,II) neuroblastoma cells from a cell-line as revealed by transmission electron microscopy (TEM). Sewing J., Klinger M., Notbohm H. Jellyfish collagen matrices conserve the chondrogenic phenotype in two- and three-dimensional collagen matrices. Hydra has already been chosen by Alan Turing in order to figure out how the chemical basis of morphogenesis can be described in a fundamental way. A switch in disulfide linkage during minicollagen assembly in Hydra nematocysts. Our results are in full agreement with AFM (Atomic Force Microscopy) and in silico studies on collagen strands interacting with proteoglycans [36]. In non-equlibrium thermodynamics [80] one has to describe the intact nematocyst in its metastable state first. Since highly malignant brain tumor cells are coated on their surfaces with polysialic acid (polySia) molecules similar like fish-eggs we use these insights for a strike against the Achilles heel of cancer cells. The experimental temperature is T in C and the experimental time is t in s. In the table on the top 45 C has been chosen as highest temperature which leads to a denaturation of the collagen strands. T3: The tumor extends into bony structure or into the area behind the nose. Fibrous minicollagens in Hydra nematocysts. Therefore, we have studied various proteoglycan fragments with molecular modelling methods concerning their interactions with collagen fragments and nematogalectins (Figure 5, Figure 6ac, Figure 8af). Why structurally different cyclic peptides can be glycomimetics of the HNK-1 carbohydrate antigen. A new increase of the temperature leads to a different profile of the values. In the case of a nematocyst discharge, which is caused by sialic acids, the chemical and physical-mechanic data can be separated . Eckert T., Sttzel S., Burg-Roderfeld M., Sewing J., Ltteke T., Nifantiev N.E., Vliegenthart J.F.G., Siebert H.-C. Accessibility Own molecular modelling calculations have shown that protein parts of proteoglycans, i.e., the leucine-rich biglycan [57,58,59] interact with other proteins in a highly specific way (Figure 7a,b). Heavy metals nematocysts discharge crude venom jellyfish pelagia. In respect to the nematocyst membrane properties (Table 1) the glycan chains are of highest interest. Federal government websites often end in .gov or .mil. Further insights concerning the boundary conditions of the discharge process in respect to material requirements and surrounding conditions are provided by biophysical experiments such as QCM (Quartz Crystal Microbalance) methods, EM - Electron Microscopy (especially TEMTransmission Electron Microscopy), AFMAtomic Force Microscopy, SPRSurface Plasmon Resonance, MSMass Spectrometry and NMRNuclear Magnetic Resonance techniques. Sialic acids trigger the initiation of the Coulomb repulsion inside the nematocyst in an intact nematocyte. Ann Emerg Med. The specificity of monoclonal anti-HNK-1 antibodies as assessed by surface plasmon resonance and NMR. Several such capsules occur on the body surface. On the left side orientation a is shown and on the right side orientation b. Therefore, this method is beside NMR, SPR and AFM experiments in combination with molecular modelling calculations [24,36,37] a valuable supporting technique when nematocyst-like medical devices have to be improved. Minicollagens are expressed from the early stages of nematocyst . As outlined by t Hooft [9]: Instruments of atomic dimensions could be used for any purpose imaginable, but particularly in medical sciences. In the case 37 C is the highest temperature (table on the bottom) no denaturation of the same material is detected. ). Cancer cells have distinct morphological parameters and a special signature of carbohydrate chains on their cell surface in which sialic acids play a prominent role. As documented in Figure 1; Figure 2 nematocyst cells from Hydra and brain-tumor cells with a high concentration of polySia molecules on their surface as well as fish-eggs with a comparable polySia density are available for complementary biophysical and biochemical experiments. Szczepanek S., Cikala M., David C.N. Our electron-microscopical (EM) analysis on nematocyst geometry has shown that the shape can be characterized as a combination of spherical and conical geometries (Figure 2). Bushman J., Mishra B., Ezra M., Gul S., Schulze C., Chaudhury S., Ripoll D., Wallqvist A., Kohn J., Schachner M., et al. The black scale bar in the lower right corner corresponds to 1 m. These carbohydrate target structures undergo specific interactions with lectins [22,38,78,94] but possibly also with carbohydrate chains [95,96,97]. Furthermore, X-ray crystallographic structure models from the protein data bank are essential to construct nematogalectin architectures which show the bridging activity of these molecules with proteoglycan fragments in the tubule cell wall. Gabius H.-J., Siebert H.-C., Andr S., Jimnez-Barbero J., Rdiger H. Chemical biology of the sugar code. Experimental data, including the parameters of various boundary conditions can be determined by a strategic combination of suited biophysical methods such as Surface Plasmon Resonance (SPR) [28], Atomic Force Microscopy (AFM) [24,37,48,73,74], nano-particle analysis supported by confocal laser scanning microscopy [75,76,77,78,79], Electron Microscopy (EM) (Figure 1 and Figure 2), NMR spectroscopy [37], Quartz Crystal Microbalance (QCM) techniques [49] (Table 1) and molecular modelling [25,36,38,39,40,41] (Figure 5, Figure 6, Figure 7 and Figure 8) provide essential biophysical data about the morphological and material characteristics of nematocysts. Determination of structural and functional overlap/divergence of five proto-type galectins by analysis of the growth-regulatory interaction with ganglioside GM1 in silico and in vitro on human neuroblastoma cells. The results shown in Table 1 indicate that the triple helical collagen strands in mixtures of collagen fragments from jellyfishes exist and can be analyzed by QCM techniques. Cai H., Chen Y., Cui X., Cai S., Chen Z. High-resolution. Why polyps regenerate and we dont: Towards a cellular and molecular framework for Hydra regeneration. Physical contact or osmotic gradient causes discharge of nematocysts; A spring loaded venom delivery system; Once opened, a nematocyst releases all of its contained venom; Clinical Features. The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages. The threshold pressure is about 3960 and all lengths are in units of the length of the stylet, please see theoretical part. The related synthetic peptides were found to refold in an oxidation process almost quantitatively into one topoisomer. Barrier to rotation around the C-sp(2)-C-sp(2) bond of the ketoaldehyde enol ether MeC(O)CH=CH-OEt as determined by 13C NMR and ab initio calculations. Chen X., Ramstrm O., Yan M. Glyconanomaterials: Emerging applications in biomedical research. This is also the case when sialic acid coated nanoparticles are studied. 2013;11(2): 523-50. It is essential to combine our theoretical results with data obtained by biophysical experiments. Nonyloxytryptamine mimics polysialic acid and modulates neuronal and glial functions in cell culture. a Rounded nematocyst vesicle at initial stage. We also thank H. Wienk and R. Boelens (Utrecht Facility for High-resolution NMR Bijvoetcenter for Biomolecular Research, University Utrecht, The Netherlands) for their support in respect of the NMR experiments (European Commissions Framework Program 7 Bio-NMR; project number 261863) as well as Philipp Siebert (RI-B-NT) for technical assistance. Unspecific associations of carbohydrate moieties from proteoglycans with collagen (Figure 5) as well as specific carbohydrate protein interactions mediated by nematogalectin (Figure 6ac) were studied with molecular modelling method in the same way as described in the literature for receptor interactions with sialic acids and sulfated carbohydrate chains [24,25,27,38]. It has to be emphasized that the polysaccharide polySia in which the sialic acid Neu5Ac building-blocks are linked by an 2-8 bond to each other are the natural triggers which are responsible for the inition of a nematocyst discharge event. Of special interest are polySia glycomimetics, e.g., Tegaserod [38,81,82], which are also interacting partners of sialic acid receptors. This experimental setting can be applied to nematocytes/nematocysts (Figure 1) but also to numerous tumor cells (Figure 2). It is possible to reference the corresponding molecular concentration and density with tailor-made sialic acid-coated nanoparticles as outlined later. Generation and regeneration of sequence of structures during morphogenesis. In an early branching metazoan, bacterial colonization of the embryo is controlled by maternal antimicrobial peptides. Benkert P., Biasini M., Schwede T. Toward the estimation of the absolute quality of individual protein structure models. The information which we derived by methods from applied and theoretical physics are sufficient to describe the complete nematocyst discharge process in its five stages. First, the inverted harpoon is packed within the capsule. Evolutionary crossroads in developmental biology: Cnidaria. Lombardi G., Della Puppa A., Zustovich F., Pambuku A., Farina P., Fiduccia P., Roma A., Zagonel V. The combination of carmustine wafers and fotemustine in recurrent glioblastoma patients: A monoinstitutional experience. The main components of the capsule wall of nematocysts, the explosive organelles of Hydra, jellyfish, corals and other Cnidaria, are collagens which are termed mini-collagens because of their shortest known collagen-like sequence of Gly-Xaa-Yaa repeats. increases nonlinearly with the pressure P (Figure 4), till at a certain threshold pressure (Pthres) = the displacement diverges, and the stylet is ejected. Heavy metals affect nematocysts discharge response and biological activity of crude venom in the jellyfish. Our theoretical model permits a discussion of the nematocyst discharge process in the dependence of key-parameters such as vessel morphologies, pressure values, forces and ejection velocities. In our case we have chosen fish eggs which have polySia in high concentration on their surface in a similar way than various tumor cells [42,43]. Mini-collagens are the major components of the Hydra nematocysts capsule wall where they form a tight three-dimensional network by disulfide reassembling of their terminal cysteine-rich domains. The first stage comprises the triggering of the cnidocil, where an external chemical-mechanical signal provides the key-signal for the Coulomb explosion. Emergen-Sea Medicine: Overview of Marine Envenomations - Page 4 of 5. WE NEED YOU! Box Jellyfish: 4-5% acetic acid solution should be applied to the injured area for at least 30 seconds. Nematocyst discharge, which is one of the fastest processes in biology, is driven by an extreme osmotic pressure of about 150 . : methodology and resources; T.E. As outlined here, corresponding experiments on triple helical collagen fragments can be performed by a combination of QCM techniques (Table 1) and molecular modelling methods (Figure 5, Figure 6ad). Zhang R., Wu L., Eckert T., Burg-Roderfeld M., Rojas-Macias M.A., Ltteke T., Krylov V.B., Argunov D.A., Datta A., Markart P., et al. Peeking into living eukaryotic cells with high-resolution NMR. However, their architecture is also of interest when nematocyts in various intact nematocytes are tested concerning its diagnostic feasibility when coming into contact with sialic acid coated surfaces. and B.N. Datta D., Talapatra S.N., Swarnakar S. An overview of lectins from freshwater and marine macroinvertebrates. Fast-growing tumor cells typically have more permeable membranes than healthy cells, allowing the leakage of marked sialic acid molecules into their cell body. Especially, the role of nematogalectins is of interest because these bridging proteins contribute as well as special collagen fibers to the elastic band properties. Furthermore, additional NMR control-experiments have been designed. Polysialic acid (polySia): Polisialic acid fragments of various chain lengths are derived from colominic acid of E. coli. As per the nematocyst definition, the phylum Cnidaria is described by the existence of this cell (sea anemones, corals, jellyfish, shydrae, etc. The dynamic genome of Hydra. 2004 ). In this context sialic acid conjugated Fluorescent Silica Nano Particles (FSNP-Sia) and functionalization of Semiconductor Quantum Dots (SQDs) with sialic acid are extremely helpful analytic tools (this will be outlined in a follow-up publication). Abstract. Sundhoro M., Park J., Jayawardana K.W., Chen X., Jayawardena H.S.N., Yan M. Poly(HEMA-co-HEMA-PFPA): Synthesis and preparation of stable micelles encapsulating imaging nanoparticles. The nematocyst capsule is filled with -glutamate polymers, which binds a 2 M concentration of cations, thereby generating a high osmotic internal pressure of more than 15 MPa [10,11]. Polysialic acid (building block: Neu5Ac-alpha2-8-Neu5Ac) in high concentration on the surface of cells (e.g., fish eggs [42] or tumor cells [25,38,43] can initiate the nematocyst discharge process. The mixture was stirred for 48 hours to give the FSNP solution. Tegaserod mimics the neurostimulatory glycan polysialic acid and promotes nervous system repair. In the second stage, a chemical trigger initiates proteolysis in the poly--glutamic acid (PGGA) resulting in an increase of the H+ concentration in the nematocyst. Beside sialic acid binding other specific carbohydrateprotein interactions play a crucial role in this study and concern nematogalectins. Sulfur-groups are highlighted by a red asterisk (*). and G.S.-B. This nano-bionic model has inspired us to analyze such processes under various boundary conditions aiming at new diagnostic and therapeutic approaches with innovative nanomedical devices. Poly-gamma-glutamate synthesis during formation of nematocyst capsules in Hydra. Cnidarians and the evolutionary origin of the nervous system. Please fill out this brief <5 minute survey to guide WikEM's development of pediatric emergency resources: https://redcapynh.ynhh.org/surveys/?s=Y7J7DDHRTNNLFFPX. the contents by NLM or the National Institutes of Health. (Anthozoa). Artificial nematocyst-like devices could be used as powerful nanomedical tool which is able to attack polySia-rich tumor cells [43]. Additionally, in the case of treatments against certain pathogens (viruses and bacteria) [39,40,41] the use of sialic acid sensitive nematocyst-like vesicles has to be considered as promising diagnostic and therapeutic option, especially, when multiresistent pathogens have to be taken into account. The 25 or more known types of nematocysts can be divided into to four functional categories: those that pierce, ensnare, or adhere to prey, and those that adhere to the substrate. These models represent typical interaction state out of a great variety of other collagen- proteoglycan complexes. In addition to discharge energy arising from osmotic pressure within the nematocyst capsule, recent work has shown that mechanisms within tubules can drive elongation, specifically osmotic potential that develops at their moving front (Park et al., 2017). Zhang R., Zhang N., Mohri M., Wu L., Eckert T., Krylov V.B., Antosova A., Ponikova S., Bednarikova Z., Markart P., et al. PubMed PMID: 29020913. The boundary conditions y()=0 and y()=0 does not aid in the solution of this nonlinear equation and does not reflect the spherical shape of the nematocyst. This approach is promising because the physical background of this process can be described in a sufficient way with formulas presented here. The mechanic-chemical contact to the sialic acid sensitive receptor is therefore responsible for non-reproducible fluctuations. Our model description of the fastest process in living nature raises and answers questions related to the material properties of the cell- and tubule-walls of nematocysts including their polysialic acid (polySia . Bar 10 m ( a ), 100 m ( b) Full size image Stenoteles of Hydra are the best-studied nematocysts (for review, see Kass-Simon and Scappaticci 2002, Thurm et al. Received 2019 Jun 1; Accepted 2019 Aug 6. Each is produced by a special cell called a cnidoblast and contains a coiled, hollow, usually barbed thread, which quickly turns outward (i.e., is everted) from the capsule upon proper stimulation. Nanomedical relevance of the intermolecular interaction dynamics-Examples from lysozymes and insulins. Different patterns of collagen-proteoglycan interaction: A scanning electron microscopy and atomic force microscopy study. Gierer A., Meinhardt H. A theory of biological pattern formation. 1 for a schematic overview of the inhibitor screen). Glycan-protein docking was performed with the Molegro 5.0 trial version. First, the inverted harpoon is packed within the capsule. We describe the discharge of the nematocyst as a five-stage process. 1 Citations 2 Altmetric Metrics Abstract Cnidarians are characterized by the possession of stinging organelles, called nematocysts, which they use for prey capture and defense. Synthesis and molecular recognition studies of the HNK-1 trisaccharide and related oligosaccharides. They are also called Cnidae and hence the coelenterates are also called Cnidarians. Firstly, PolySia specific targeting by lectins, especially, mini-lectins which mimic the receptors on the nematocyst surface must be defined in detail [25,38,39,48]. Krieger E., Vriend G. YASARA Viewmolecular graphics for all devices-from smartphones to workstations. Ultrathin sections (100 ) were contrasted with lead citrate (2%) and uranylacetate (0.5%) and examined in a Zeiss 109 electron microscope. If the stationary state of the process is metastable, then non-reproducible fluctuations involve local transient decreases of entropy. where V is the volume of the nematocyst and U is the internal energy (electrostatic potential energy). Therefore, the structural elements responsible for their distinct structures were analyzed to gain possible information about the mechanisms of mini-collagen disulfide rearrangement in their assembly into polymeric fibers. Polysialic acid is present in mammalian semen as a post-translational modification of the neural cell adhesion molecule NCAM and the polysialyltransferase ST8SiaII. Holdt S.L., Kraan S. Bioactive compounds in seaweed: Functional food applications and legislation. The stylets of the nematocysts are ejected by a specific biological signal (sialic acids, especially polySia) which is present on fish eggs but also on various tumor cells [42,43]. A potential application in nanomedicine is possible since polySia occurs also in high concentration in the glycocalyx of tumor cells and are responsible for their degree of malignancy. Tursch A., Mercadante D., Tennigkeit J., Grater F., zbek S. Minicollagen cysteine-rich domains encode distinct modes of polymerization to form stable nematocyst capsules. This further pushes out the stylet thereby locking it with barbs in the victim or in some cases disposes off the outer sheath of the stylet. Hitherto, the molecular basis for the unusual biomechanical properties of nematocysts has been elusive, as their structure was mainly defined as a stress-resistant collagenous matrix. It has to be emphasized that the source (e.g., fish or jellyfish) is not important for the occurrence of larger fragments but for the special production process. Lenhoff H.M., Brown R.D. Watanabe H., Fujisawa T., Holstein T.W. R.Z. (2021, April 23). The matrix component biglycan is proinflammatory and signals through Toll-like receptors 4 and 2 in macrophages [57,58,59]. Furthermore, the initial release mechanism triggered by an interaction of cell-surface exposed receptor with sialic acid molecules can be studied in detail using biophysical methods in combination with suited model systems [25,38,41,42]. Adamczyk P., Zenkert C., Balasubramanian P.G., Yamada S., Murakoshi S., Sugahara K., Hwang J.S., Gojobori T., Holstein T.W., zbek S. A non-sulfated chondroitin stabilizes membrane tubulation in cnidarian organelles. The nematocyst is a complex intracellular structure unique to Cnidaria. Structure-function relationships of antimicrobial peptides and proteins with respect to contact molecules on pathogen surfaces. The .gov means its official. FSNP-Sia was synthesized using fluorescein-doped silica nanoparticles (FSNP) and the photocoupling strategy to conjugate Sia on FSNP, following previously developed protocols [75,76,77,78,79,107]. Experiments were carried out using Hydra vulgaris strain AEP. The Once and Future Turing: Computing the World. The threshold pressure is proportional to the elastic modulus (Y) of the capsule and hence the exit orifice. Soriano J., Rudiger S., Pullarkat P., Ott A. Mechanogenetic coupling of Hydra symmetry breaking and driven Turing instability model.
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