Nature Of Cross-links Research Articles

Lysyl hydroxylase 2 induces a collagen cross-link switch in tumor stroma.

Epithelial tumor metastasis is preceded by an accumulation of collagen cross-links that heighten stromal stiffness and stimulate the invasive properties of tumor cells. However, the biochemical nature of collagen cross-links in cancer is still unclear. Here, we postulated that epithelial tumorigenesis is accompanied by changes in the biochemical type of collagen cross-links. Utilizing resected human lung cancer tissues and a p21CIP1/WAF1-deficient, K-rasG12D-expressing murine metastatic lung cancer model, we showed that, relative to normal lung tissues, tumor stroma contains higher levels of hydroxylysine aldehyde-derived collagen cross-links (HLCCs) and lower levels of lysine aldehyde-derived cross-links (LCCs), which are the predominant types of collagen cross-links in skeletal tissues and soft tissues, respectively. Gain- and loss-of-function studies in tumor cells showed that lysyl hydroxylase 2 (LH2), which hydroxylates telopeptidyl lysine residues on collagen, shifted the tumor stroma toward a high-HLCC, low-LCC state, increased tumor stiffness, and enhanced tumor cell invasion and metastasis. Together, our data indicate that LH2 enhances the metastatic properties of tumor cells and functions as a regulatory switch that controls the relative abundance of biochemically distinct types of collagen cross-links in the tumor stroma.

Statistically Designed High and Low Methyl Acrylate (Ma) Containing Ema-Ethylene-Octene Copolymer Double Network Hybrids: Interesting Contrast in Physico-Mechanical, Rheological and Electrical Properties

This paper demonstrates interesting contrasts between physical, mechanical and rheological properties of double network hybrids developed from high (30 wt.%) and low (9 wt.%) methyl acrylate containing poly (ethylene-co-methyl acrylate) and poly (ethylene-co-octene) thermoplastic elastomer. The compositions were designed adopting a Taguchi L9 statistical model. The model was espoused to consider a wide range of blend compositions and process conditions for optimization. The majority of the low methyl acrylate containing hybrids showed normal correlation between mechanical and other physical properties with the net gel content while for the other variety, they were ambiguous. The reason was investigated and it was found to be due to the influence of the nature of crosslinks formed between the phases which controlled the properties in the latter. Based on the results, finally, two blend compositions were chosen from each set as the most optimized formulations for future study.

Engineering novel polyelectrolyte complex membranes with improved mechanical properties and separation performance

Polyelectrolyte complexes (PECs) commonly suffer from poor processability owing to their ionic crosslinking nature, a problem which spurs increasing interest in processable PECs.

Mimicking the hierarchical functions of dentin collagen cross-links with plant derived phenols and phenolic acids.

Proanthocyanidins (PACs) are secondary plant metabolites that mediate nonenzymatic collagen cross-linking and enhance the properties of collagen based tissue, such as dentin. The extent and nature of cross-linking is influenced by the composition and specific chemical structure of the bioactive compounds present in certain PAC-rich extracts. This study investigated the effect of the molecular weight and stereochemistry of polyphenol compounds on two important properties of dentin, biomechanics, and biostability. For that, purified phenols, a phenolic acid, and some of its derivatives were selected: PAC dimers (A1, A2, B1, and B2) and a trimer (C1), gallic acid (Ga), its esters methyl-gallate (MGa) and propyl-gallate (PGa), and a pentagalloyl ester of glucose (PGG). Synergism was assessed by combining the most active PAC and gallic acid derivative. Mechanical properties of dentin organic matrix were determined by the modulus of elasticity obtained in a flexural test. Biostability was evaluated by the resistance to collagenase degradation. PACs significantly enhanced dentin mechanical properties and decreased collagen digestion. Among the gallic acid derivatives, only PGG had a significant enhancing effect. The lack of observed C1:PGG synergy indicates that both compounds have similar mechanisms of interaction with the dentin matrix. These findings reveal that the molecular weight of polyphenols have a determinant effect on their interaction with type I collagen and modulates the mechanism of cross-linking at the molecular, intermolecular, and inter-microfibrillar levels.

Effect of Biochar bead on Adsorption of Heavy Metals

In recent years, biochar has received much attention as soil amendment, enhancing soil fertility and reducing toxicity of heavy metals with its large specific surface area and high pH. Biochar has also the effect of alleviating global warming by carbon sequestration from recycling organic wastes by pyrolysis. However, scattering of fine particles of biochar is a hindrance to expand its use from human health point-of-view. Alginate, a natural polymer without toxicity, has been used for capsulation and hydrogel fabrication due to its cross-linking nature with calcium ion. In this study, the method of cross-linkage between alginate and calcium ion was employed for making dust-free biochar bead. Then an equilibrium adsorption experiment was performed for verifying the adsorption effect of biochar bead on heavy metals (cadmium, copper, lead, arsenic, and zinc). Results showed that biochar bead had effects on adsorbing heavy metals, especially lead, except arsenic.

Multilayered polymer capsules with switchable permeability

The preparation of layer-by-layer (LbL) polymer capsules stabilized by a combination of copper-catalyzed azide-alkyne cycloaddition (CuAAC, “click chemistry”) and disulfide cross-linking is reported. The capsules obtained possess gated permeability due to the reversible nature of the disulfide cross-linking. Poly(methacrylic acid) (PMA) was modified with different ratios of alkyne and protected thiol functionalities (PMAAlk,SH). Exploiting hydrogen bonding interactions, multilayered films were prepared by the alternate deposition of PMAAlk,SH (hydrogen bonding donor) and poly(N-vinylpyrrolidone) (PVPON; hydrogen bonding acceptor), yielding stable PMAAlk,SH capsules. Capsule pH responsive behavior and permeability, using a series of different size and labeled dextrans, were investigated in both the “closed” state (disulfide cross-linking intact) and “open” state (free thiol groups). To demonstrate the potential of these gateable systems, post-loading studies with fluorescent 45-base pair (bp) linear double-stranded (ds) DNA were performed. Fluorescence studies revealed the potential of these capsules to reversibly encapsulate cargo: cleavage and reformation of the disulfide groups resulted in reversible permeability to the DNA.

Thermal behaviour of bis-benzoxazines derived from renewable feed stock 'vanillin'

Several bis-benzoxazine monomers (Va-BBz)s were synthesized using a naturally occurring phenol: vanillin, different diamines such as ethylene diamine (EDA), diaminodiphenyl sulphone (DDS), diaminodiphenyl ether (DDE), diaminodiphenyl methane (DDM) and 2,2′-bis [4-(4-aminophenoxy)phenyl] propane (BAPP) and paraformaldehyde. The structure of the bis-benzoxazine monomers was characterized by FT-IR, 1H and 13C NMR. The effect of structure on curing behaviour and thermal properties was evaluated by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The poly(bis-benzoxazine)s derived from vanillin had high Tg (202–255 °C), high char yield (52–76%) and excellent thermal stability due to highly cross-linked nature of the polymer. Adhesive strength of cured resins (i.e. poly(Va-BBz)s) were also evaluated at 200 °C.

Fabrication of conductive elastic nanocomposites via framing intact interconnected graphene networks

Electrically conductive elastic nanocomposites with well-organized graphene architectures offer significant improvement in various properties. However, achieving desirable graphene architectures in cross-linked rubber is challenging due to high viscosity and cross-linked nature of rubber matrices. Here, three dimensional (3D) interconnected graphene networks in natural rubber (NR) matrix are framed with self-assembly integrating latex compounding technology by employing electrostatic adsorption between poly(diallyldimethylammonium chloride) modified graphene (positively charged) and NR latex particles (negatively charged) as the driving force. The 3D graphene structure endows the resulted nanocomposites with excellent electrical conductivity of 7.31 S/m with a graphene content of 4.16 vol.%, extremely low percolation threshold of 0.21 vol.% and also analogous reinforcement in mechanical properties. The developed strategy will provide a practical approach for developing elastic nanocomposites with multi-functional properties.

Fluorinated Porous Poly(spirobifluorene) Via Direct C‒H Arylation: Characterization, Porosity, and Gas Uptake

Considering intrinsic properties of conjugated polyfluorenes and special functions of porous polymers, synthesis of fluorinated porous poly(spirobifluorene) via direct C−H arylation polycondensation is explored. Owing to the contorted structure and cross-linking nature, the obtained polymer FPSBF shows permanent porosities with Brunauer–Emmett–Teller specific surface area up to 700 m2 g−1 and exhibits a narrow pore size distribution with the dominant pore size at about 0.63 nm, which is more suitable for adsorption of small gas molecules. Based on the measured gas physisorption isotherms with pressure up to 1.13 bar, the obtained polymer shows good uptaking capacities for hydrogen (1.30 wt% at 1.0 bar and 77 K) and methane (4.80 wt% 1.0 bar and 273 K). Moreover, FPSBF has significant adsorption selectivity for CH4 against N2 and the estimated ideal adsorption selectivity ratio is up to 30/1 at 1.0 bar and 273 K, which makes the material possess potential application in gas separation.

Discovery and characterization of a photo-oxidative histidine-histidine cross-link in IgG1 antibody utilizing ¹⁸O-labeling and mass spectrometry.

A novel photo-oxidative cross-linking between two histidines (His-His) has been discovered and characterized in an IgG1 antibody via the workflow of XChem-Finder, 18O labeling and mass spectrometry (Anal. Chem.2013, 85, 5900−590823634697). Its structure was elucidated by peptide mapping with multiple proteases with various specificities (e.g., trypsin, Asp-N, and GluC combined with trypsin or Asp-N) and mass spectrometry with complementary fragmentation modes (e.g., collision-induced dissociation (CID) and electron-transfer dissociation (ETD)). Our data indicated that cross-linking occurred across two identical conserved histidine residues on two separate heavy chains in the hinge region, which is highly flexible and solvent accessible. On the basis of model studies with short peptides, it has been proposed that singlet oxygen reacts with the histidyl imidazole ring to form an endoperoxide and then converted to the 2-oxo-histidine (2-oxo-His) and His+32 intermediates, the latter is subject to a nucleophilic attack by the unmodified histidine; and finally, elimination of a water molecule leads to the final adduct with a net mass increase of 14 Da. Our findings are consistent with this mechanism. Successful discovery of cross-linked His-His again demonstrates the broad applicability and utility of our XChem-Finder approach in the discovery and elucidation of protein cross-linking, particularly without a priori knowledge of the chemical nature and site of cross-linking.

Crosslinking of Isabgol husk polysaccharides for microspheres development and its impact on particle size, swelling kinetics and thermal behavior

The microspheres were prepared by emulsification method using glutaraldehyde as crosslinker. The effects of variables as temperature, concentration of Isabgol husk and glutaraldehyde, and nature of dispersing media were analyzed on microsphere-derived properties such as size distribution, surface morphology, and swelling kinetics. The nature of crosslinking and interaction of polysaccharides structure with glutaraldehyde were assessed by thermal analysis and infrared spectroscopy. The spherical and free flowing microspheres were obtained and a significant effect of process variables was observed on characteristics of formulations. The microspheres revealed their potential in the development of sustained release drug carriers for water soluble/insoluble drugs.

Re-use assessment of thermoset composite wastes as aggregate and filler replacement for concrete-polymer composite materials: A case study regarding GFRP pultrusion wastes

Glass fibre-reinforced plastics (GFRP), nowadays commonly used in the construction, transportation and automobile sectors, have been considered inherently difficult to recycle due to both the cross-linked nature of thermoset resins, which cannot be remoulded, and the complex composition of the composite itself, which includes glass fibres, polymer matrix and different types of inorganic fillers. Hence, to date, most of the thermoset based GFRP waste is being incinerated or landfilled leading to negative environmental impacts and additional costs to producers and suppliers. With an increasing awareness of environmental matters and the subsequent desire to save resources, recycling would convert an expensive waste disposal into a profitable reusable material. In this study, the effect of the incorporation of mechanically recycled GFRP pultrusion wastes on flexural and compressive behaviour of polyester polymer mortars (PM) was assessed. For this purpose, different contents of GFRP recyclates (0%, 4%, 8% and 12%, w/w), with distinct size grades (coarse fibrous mixture and fine powdered mixture), were incorporated into polyester PM as sand aggregates and filler replacements. The effect of the incorporation of a silane coupling agent was also assessed. Experimental results revealed that GFRP waste filled polymer mortars show improved mechanical behaviour over unmodified polyester based mortars, thus indicating the feasibility of GFRP waste reuse as raw material in concrete-polymer composites.

Physicochemical studies of crosslinked thiolated polyvinyl alcohol hydrogels

This study is related to the post-crosslinking of thiolated polyvinyl alcohol (TPVA) hydrogels using three crosslinkers, sodium trimetaphosphate (STMP), boric acid (BA) and glyoxal (GLY) under alkaline conditions. The crosslinking reaction was carried out under different conditions: crosslinker nature, crosslinker content and crosslinking time. The influence of different crosslinkers on the physicochemical and structural characteristics of TPVA was evaluated. The three reagents used for crosslinking presented different action mode on hydrogels. The optimized crosslinking conditions were the crosslinker content is 0.1 % (w/v) at crosslinking time of 30 min. The results showed that the STMP-crosslinked TPVA had the maximum thiol content and swelling ability. All crosslinked TPVA samples were stable in different pH media. The involvement of thiol and other relevant groups after crosslinking in the different crosslinked TPVA samples was confirmed by attenuated total reflectance-infrared spectra. The microanalysis of elements present in the crosslinked samples were analyzed by energy-dispersive X-ray microanalysis.

Discovery of undefined protein cross-linking chemistry: a comprehensive methodology utilizing 18O-labeling and mass spectrometry.

Characterization of protein cross-linking, particularly without prior knowledge of the chemical nature and site of cross-linking, poses a significant challenge, because of their intrinsic structural complexity and the lack of a comprehensive analytical approach. Toward this end, we have developed a generally applicable workflow-XChem-Finder-that involves four stages: (1) detection of cross-linked peptides via (18)O-labeling at C-termini; (2) determination of the putative partial sequences of each cross-linked peptide pair using a fragment ion mass database search against known protein sequences coupled with a de novo sequence tag search; (3) extension to full sequences based on protease specificity, the unique combination of mass, and other constraints; and (4) deduction of cross-linking chemistry and site. The mass difference between the sum of two putative full-length peptides and the cross-linked peptide provides the formulas (elemental composition analysis) for the functional groups involved in each cross-linking. Combined with sequence restraint from MS/MS data, plausible cross-linking chemistry and site were inferred, and ultimately confirmed, by matching with all data. Applying our approach to a stressed IgG2 antibody, 10 cross-linked peptides were discovered and found to be connected via thioethers originating from disulfides at locations that had not been previously recognized. Furthermore, once the cross-link chemistry was revealed, a targeted cross-link search yielded 4 additional cross-linked peptides that all contain the C-terminus of the light chain.

Investigation of potential injectable polymeric biomaterials for bone regeneration

This article reviews the potential injectable polymeric biomaterial scaffolds currently being investigated for application in bone tissue regeneration. Two types of injectable biomaterial scaffolds are focused in this review, including injectable microspheres and injectable gels. The injectable microspheres section covers several polymeric materials, including poly(L-lactide-co-glycolide)-PLGA, poly(propylene fumarate), and chitosan. The injectable gel section covers alginate gels, hyaluronan hydrogels, poly(ethylene-glycol)-PEG hydrogels, and PEG-PLGA copolymer hydrogels. This review focuses on the effect of cellular behavior in vitro and in vivo in terms of material properties of polymers, such as biodegradation, biocompatibility, porosity, microsphere size, and cross-linking nature. Injectable polymeric biomaterials offer a major advantage for orthopedic applications by allowing the ability to use noninvasive or minimally invasive treatment methods. Therefore, combining injectable polymeric biomaterial scaffolds with cells have a significant potential to treat orthopedic bone defects, including spine fusion, and craniofacial and periodontal defects.

On the Formation and Properties of Interstrand DNA–DNA Cross-Links Forged by Reaction of an Abasic Site with the Opposing Guanine Residue of 5′-CAp Sequences in Duplex DNA

We recently reported that the aldehyde residue of an abasic (Ap) site in duplex DNA can generate an interstrand cross-link via reaction with a guanine residue on the opposing strand. This finding is intriguing because the highly deleterious nature of interstrand cross-links suggests that even small amounts of Ap-derived cross-links could make a significant contribution to the biological consequences stemming from the generation of Ap sites in cellular DNA. Incubation of 21-bp duplexes containing a central 5'-CAp sequence under conditions of reductive amination (NaCNBH(3), pH 5.2) generated much higher yields of cross-linked DNA than reported previously. At pH 7, in the absence of reducing agents, these Ap-containing duplexes also produced cross-linked duplexes that were readily detected on denaturing polyacrylamide gels. Cross-link formation was not highly sensitive to reaction conditions, and the cross-link, once formed, was stable to a variety of workup conditions. Results of multiple experiments including MALDI-TOF mass spectrometry, gel mobility, methoxyamine capping of the Ap aldehyde, inosine-for-guanine replacement, hydroxyl radical footprinting, and LC-MS/MS were consistent with a cross-linking mechanism involving reversible reaction of the Ap aldehyde residue with the N(2)-amino group of the opposing guanine residue in 5'-CAp sequences to generate hemiaminal, imine, or cyclic hemiaminal cross-links (7-10) that were irreversibly converted under conditions of reductive amination (NaCNBH(3)/pH 5.2) to a stable amine linkage. Further support for the importance of the exocyclic N(2)-amino group in this reaction was provided by an experiment showing that installation of a 2-aminopurine-thymine base pair at the cross-linking site produced high yields (15-30%) of a cross-linked duplex at neutral pH, in the absence of NaCNBH(3).

Thermoresponsive Dynamic Covalent Single‐Chain Polymer Nanoparticles Reversibly Transform into a Hydrogel

To gel and back: Polymer nanoparticles can be reversibly transformed into a chemically cross-linked hydrogel. This transformation is triggered by the application of heat, which causes the polymer chains to aggregate, and the dynamic nature of the covalent cross-linking serves to reorganize the polymer chains into a hydrogel network.

Kinetic Study on the Reduction Reaction of Biomass-Tar-Infiltrated Iron Ore

This work describes a new biomass ironmaking that uses low-grade iron ore and woody biomass for promoting the direct reduction of a nanoporous iron ore infiltrated and carbonized with biomass tar (biotar). The mechanism and kinetics of the reduction reaction of the carbon-infiltrated ore were systematically studied by means of thermogravimetric analysis with X-ray diffraction (XRD) and Raman scattering spectrometry. The results showed that the carbon-infiltrated ore reduced at a significantly lower temperature than the mixture of reagent magnetite and metallurgical coke. It was confirmed that this high reactivity was due to the nanoscale contact between carbon and the ore and the less fused and less cross-linked nature of the biotar-derived carbon. From the combination of thermogravimetry and XRD analyses, it is revealed that the reduction reaction occurred serially in three steps: re-evaporation and/or carbonization of biotar, reduction of magnetite to wustite, and reduction of wustite to iron. Finally, ...

Isolation of suberin from birch outer bark and cork using ionic liquids: A new source of macromonomers

Cholinium hexanoate, a biocompatible and biodegradable ionic liquid, was recently demonstrated to efficiently and selectively extract suberin domains from cork, combining high extraction efficiency with isolation of a partial depolymerised material. In the present paper, we report a comparative study of the characterisation of suberin extracted from birch outer bark and from cork using cholinium hexanoate. It became apparent that both extracted suberin samples showed still a cross-linked nature, i.e. likely to be closely related to in situ suberin. Suberin samples were mainly constituted by oligomeric or polymeric structures in turn essentially composed by long chain hydroxyacids monomers. Their high thermal stability together with the oligomeric/polymeric nature, open new perspectives for suberin use as macromonomers in the development of bio-based polymeric materials. This also contributes for the valorisation of suberin rich agro-forest residues.

METAL AND METAL-SULPHIDE CONTAINING CARBONS FROM SULPHONATED STYRENE-DIVINYLBENZENE COPOLYMER BASED ION-EXCHANGERS

A temperature controlled carbonization process (5-800 °C for 1-4 h) of metal forms of various types of partially or completely saturated sulphonated styrene-divinylbenzene copolymer based ion-exchangers loaded with various valence state metal ions has been evaluated. The effect of temperature, nature and valence of metal ions, cross-linking and other parameters on the composition and properties of the synthesised composites have been evaluated. Depending on the ionic form and the degree of saturation of the ion exchangers the sulphur content of the ion-exchangers can partially transform into metal sulphides, SO 3 or SO 2 . Ni(II), Mn(II) and Zn(II) forms of the ion-exchangers resulted the appropriate M II S type metal sulphides (NiS, MnS or ZnS), while copper(II) resulted metallic copper formation at 500 °C in 2 h. Both iron(II) and iron(III) forms of sulphonated styrene-divinylbenzene copolymers resulted Fe 0.95 S and a-Fe formation at 800 °C for 2 h, however, the ratio of these compounds depended on the valence state of iron and were found to be 8:1 and 7:2 in the case of Fe(III) and Fe(II)-forms, respectively. The shape of the so formed carbon particles are bead-like and the hardness of the formed carbon beads proportional with the divinylbenzene content of the starting polymer. The higher divinylbenzene content the harder beads of carbon forms. All the beads have a leakage path due to evolution of gases which emitted at the weakest part of ball-like bead. The ball-like metal-containing activated carbon beads have low hydrodynamic resistance towards fluid streams and this carbonisation method can be used as an environmentally friendly way for processing of waste ion-exchangers into industrially usable carbon based metallic containing composites.