Connector Molecules Research Articles

An MD study of the polymer–polymer adhesion via connector chains: some aspects of the competition between bulk dissipation in the interphase and pull-out of interface-connecting molecules

Atomistic simulation approach was used to analyze the separation behavior of polymer–polymer interfaces. This was achieved using coarse-grained molecular dynamics (MD) simulations of some connector chains embedded in two adjacent polymer entangled melts. To separate the contribution of polymer molecules pull-out from the micro-bulk dissipation in the viscoplastic interphase, surrounding the surface of separation, two kinds of simulations were considered: (a), simulations of the pull-out mechanism, where the extraction of the connectors out of the melts takes place through a complex mechanism of forced reptation only; (b), simulations of the full debonding process where the micro-bulk dissipation contributes to the overall crack opening and can skew the description of the interface separation by pure connector molecules pull-out. From the MD simulation results, some relevant parameters (e.g., a cohesive strength or an adhesion energy) of the separation behavior of the interface being modelized were extracted. In addition, one was able to separate quantitatively connector pull-out from micro-bulk dissipation (in the surrounding bulk region of the interface). This means that we were able to emphasize: (i) how the straining divides into interface opening and bulk deformation and (ii), how the macroscopic opening rate diffuses throughout the melts and the interface opening rate, since the mechanical behavior of polymers is strain-rate dependent. A comparison between two kinds of MD simulations, where a system is stretched along one direction, is shortly discussed as a necessary prelude to future investigations.

Discovery of new candidate genes for rheumatoid arthritis through integration of genetic association data with expression pathway analysis

BackgroundHere we integrate verified signals from previous genetic association studies with gene expression and pathway analysis for discovery of new candidate genes and signaling networks, relevant for rheumatoid arthritis (RA).MethodRNA-sequencing-(RNA-seq)-based expression analysis of 377 genes from previously verified RA-associated loci was performed in blood cells from 5 newly diagnosed, non-treated patients with RA, 7 patients with treated RA and 12 healthy controls. Differentially expressed genes sharing a similar expression pattern in treated and untreated RA sub-groups were selected for pathway analysis. A set of “connector” genes derived from pathway analysis was tested for differential expression in the initial discovery cohort and validated in blood cells from 73 patients with RA and in 35 healthy controls.ResultsThere were 11 qualifying genes selected for pathway analysis and these were grouped into two evidence-based functional networks, containing 29 and 27 additional connector molecules. The expression of genes, corresponding to connector molecules was then tested in the initial RNA-seq data. Differences in the expression of ERBB2, TP53 and THOP1 were similar in both treated and non-treated patients with RA and an additional nine genes were differentially expressed in at least one group of patients compared to healthy controls. The ERBB2, TP53. THOP1 expression profile was successfully replicated in RNA-seq data from peripheral blood mononuclear cells from healthy controls and non-treated patients with RA, in an independent collection of samples.ConclusionIntegration of RNA-seq data with findings from association studies, and consequent pathway analysis implicate new candidate genes, ERBB2, TP53 and THOP1 in the pathogenesis of RA.

Motors, anchors, and connectors: orchestrators of organelle inheritance.

Organelle inheritance is a process whereby organelles are actively distributed between dividing cells at cytokinesis. Much valuable insight into the molecular mechanisms of organelle inheritance has come from the analysis of asymmetrically dividing cells, which transport a portion of their organelles to the bud while retaining another portion in the mother cell. Common principles apply to the inheritance of all organelles, although individual organelles use specific factors for their partitioning. Inheritance factors can be classified as motors, which are required for organelle transport; anchors, which immobilize organelles at distinct cell structures; or connectors, which mediate the attachment of organelles to motors and anchors. Here, we provide an overview of recent advances in the field of organelle inheritance and highlight how motor, anchor, and connector molecules choreograph the segregation of a multicopy organelle, the peroxisome. We also discuss the role of organelle population control in the generation of cellular diversity.

Friction mediated by redox-active supramolecular connector molecules.

We report on a friction study at the nanometer scale using atomic force microscopy under electrochemical control. Friction arises from the interaction between two surfaces functionalized with cyclodextrin molecules. The interaction is mediated by connector molecules with (ferrocenylmethyl)ammonium end groups forming supramolecular complexes with the cyclodextrin molecules. With ferrocene connector molecules in solution, the friction increases by a factor of up to 12 compared to control experiments without connector molecules. The electrochemical oxidation of ferrocene to ferrocenium causes a decrease in friction owing to the lower stability of ferrocenium-cyclodextrin complex. Upon switching between oxidative and reduction potentials, a change in friction by a factor of 1.2-1.8 is observed. Isothermal titration calorimetry reveals fast dissociation and rebinding kinetics and thus an equilibrium regime for the friction experiments.

Dynamic effects in friction and adhesion through cooperative rupture and formation of supramolecular bonds.

We introduce a molecular toolkit for studying the dynamics in friction and adhesion from the single molecule level to effects of multivalency. As experimental model system we use supramolecular bonds established by the inclusion of ditopic adamantane connector molecules into two surface-bound cyclodextrin molecules, attached to a tip of an atomic force microscope (AFM) and to a flat silicon surface. The rupture force of a single bond does not depend on the pulling rate, indicating that the fast complexation kinetics of adamantane and cyclodextrin are probed in thermal equilibrium. In contrast, the pull-off force for a group of supramolecular bonds depends on the unloading rate revealing a non-equilibrium situation, an effect discussed as the combined action of multivalency and cantilever inertia effects. Friction forces exhibit a stick-slip characteristic which is explained by the cooperative rupture of groups of host-guest bonds and their rebinding. No dependence of friction on the sliding velocity has been observed in the accessible range of velocities due to fast rebinding and the negligible delay of cantilever response in AFM lateral force measurements.

The Mechanism of Adhesion Improvement of Elastomeric Silicone Sealants to Difficult-to-Bond Polymeric Substrates through Reactive or Interpenetrating Molecular Brushes

Abstract High-quality and durable adhesion of elastomeric adhesives to metallic, ceramic, and organic substrates is essential to a broad range of industries, e.g., building and construction, automotive, electronic, aerospace, biomedical, and others. The principles of engineering substrate surfaces through grafted connector molecules are discussed in this paper. In particular, two important modes of interaction for surface-grafted “molecular brushes” are investigated and experimentally verified. It is demonstrated that the inclusion of silicone- and/or amine-terminated graft molecules, such as silanes or polyethyleneimines, at polymer interfaces, results in the formation of strong molecular bridges between a range of organic substrates and elastomeric sealants leading to significantly improved bonding. The technology has been successfully adopted by global automotive industry for improving adhesion of a variety of adhesives and coatings to polyolefinic substrates.

Self-Assembly of Heptameric Nanoparticles Derived from Tag-Functionalized Phi29 Connectors

The structure of an induced macromolecular assembly was characterized and found to consist of an ordered heptameric arrangement of recombinant phi29 gp10 connector molecules. Insertion of an N-terminal Strep-II/His(6) tag to the connectors led to the spontaneous formation of large nanoparticles that were distinct from free, wild-type phi29 connectors in both size and symmetry elements. The determination of single-molecule tomograms and image-averaged reconstructions allowed for the stoichiometric and topological characterization of the ordered assemblage, revealing that the nanoparticle is composed of five equatorial connectors arranged with pseudo-5-fold rotational symmetry, capped on its ends by two polar connectors. Additionally, all seven connectors are oriented with their narrower N-terminal necks into the nanoparticle core and wider C-terminal ends out toward the nanoparticle surface, a geometric arrangement accommodated by the shape complementarity of the conical connector profiles. A significant amount of conformational heterogeneity was detected, ranging from changes in overall nanoparticle diameter, to tilting of individual connectors, to variations in connector stoichiometry. Nevertheless, a stable, heptameric nanoparticle was resolved, revealing the significant potential of guided, peptide-mediated supramolecular self-assembly. With this construct, we anticipate the further design of variable N-terminal tags to allow for the generation of nanoparticles with tailored connector stoichiometry and topological arrangements. By modifying the surface-exposed C-terminal ends with application-appropriate moieties, the consistent structure and compact nature of these nanoparticles may prove beneficial in nanotechnological and nanomedical approaches.

Selective Assembly of Multi-Component Nanosprings and Nanorods

This communication proposes a new approach to create complex hierarchical nano-to-meso-scale architectures based on the use of biological connector molecules to direct the assembly of uniquely shaped multi-component nanostructures fabricated using glancing angle deposition (GLAD). Multiple sets of 50-nm-wide and 150 to 650-nm-tall Si-Cr/Au multi-stack zigzag nanosprings and nanorods are grown by GLAD on Si substrates. Nanorods, chosen for selective assembly, are detached from the substrate, suspended in an aqueous solution, and their surfaces are selectively functionalized by attaching biotin and streptavidin connector-molecules to the Au-regions. Successive mixing of different suspensions leads to the end-to-end assembly of long and short nanorods. This technique provides the path to build hybrid nano-architectures including nano-honeycombs, nanoladders, and 3D nanorod networks, comprised of controlled material combinations.

The influence of loose and semianchored siloxane polymer chains on the tack of crosslinked silicone rubber

AbstractThe influence of addition of nonreactive silicone oil or semianchored silicone polymer on crosslinked poly(dimethylsiloxane) (PDMS) rubber–rubber adhesion was studied. The additives can be considered either a tackifier, or connector molecules, able to cross the interface and entangle. In both cases, it influences the tack of the elastomers. An additional variable is the molecular weight of the additive, which affects the reptation of the polymer chains. Polymer–polymer demixing, which is the result of thermodynamic incompatibility of mixed polymers is another factor that influences tack. It causes the free chains to appear at the surface forming a layer of oil, which actually destroys the tack of the PDMS samples. The resulting tack phenomena as a function of oil, respectively semianchored silicone polymer chains, are very much dependent on the transient nature of the polymer reptation: in many cases the polymers need very long time periods to obtain equilibrium in interphase crossing, or oil sweats out of the crosslinked polymers, forming a liquid layer between the two phases resulting in a low tack value, due to hydrodynamic wetting alone. © 2009 Wiley Periodicals, Inc. J Appl Polym Sci, 2009

Adhesion mechanisms at soft polymer interfaces

Based on several significant examples, we analyse the adhesion mechanisms at soft polymer interfaces with a special emphasis first on the role of connector molecules, that is, polymer chains bound to the interface and which transmit stress through a stretching and extraction mechanism, and second on the necessary relay that must be taken by additional dissipation mechanisms acting at larger scales if one wants to reach typical fracture toughnesses in the range of a few 10 J m(-2). Examples of such bulk dissipation mechanisms will be discussed for interfaces between polymer melts and for pressure-sensitive adhesives in contact with a solid surface. We shall particularly point out the fact that the level of adhesion results from a competition between adhesive failure usually driven by both the interactions and the friction properties of the interface and bulk strong deformations which take place in the bulk of the adhesive layer. Controlling the friction properties of the interface then becomes a tool to finely tune adhesive properties.

The influence of structure of the interface and interphase on paint adhesion

It has been demonstrated earlier that significant adhesion enhancement to chemically inert polyolefins can be attained through surface grafted connector molecules reactive with oxidized substrate surface. The effectiveness of adhesion improvement through such tethered interfaces was shown to depend on the mode of interaction with the adjacent medium: interpenetration or chemical reaction, as well as surface density and length of grafted molecules. We have frequently observed that some systems, such as in painted products, fail through the delamination of the coating from the substrate surface at the stress levels well below the anticipated load-bearing capacity of the tethered interface. Two interim hypotheses have been formulated to explain the observed phenomenon: (i) The chain scission in surface oxidized polyolefins takes place not only in the uppermost polymer surface, but may propagate into the sub-surface region, thus creating a weak boundary layer which fails cohesively through its bulk, (ii) In order to increase the load-bearing capacity of the interphase, the sub-surface region of the substrate needs to be reinforced by short-chain molecules penetrating into and subsequently providing effective crosslinks between individual fragments of excessively oxidized and hence, weaker sub-surface part of the interphase. In this paper we verify the above hypotheses. The oxidized sub-surface layer reinforced by polyethyleneimine becomes an integral part of the effective interphase in addition to the tethered interface and the interpenetrated network of connector molecules and the paint.

Interface/interphase engineering of polymers for adhesion enhancement: Part II. Theoretical and technological aspects of surface-engineered interphase-interface systems for adhesion enhancement

Part I of this paper reviewed the theoretical principles of the macromolecular design of polymer interface/interphase systems for obtaining maximum adhesion and fracture performance of adhesively bonded assemblies. In Part II a novel, relatively simple and industry-feasible technology for surface-grafting connector molecules is demonstrated and discussed in detail and supported by a range of experimental examples. It is shown, in agreement with contemporary theory, that the use of chemically attached graft chemicals of controlled spatial geometry and chemical functionality enables a significant increase in the strength and fracture energy of the interphase, to the point of cohesive fracture of the substrate, or that of an adjacent medium such as adhesive, elastomer, or other material. This occurs even after prolonged exposure of investigated systems to adverse environments such as hot water.

Structure determination of the head-tail connector of bacteriophage phi29.

The head-tail connector of bacteriophage phi29 is composed of 12 36 kDa subunits with 12-fold symmetry. It is the central component of a rotary motor that packages the genomic dsDNA into preformed proheads. This motor consists of the head-tail connector, surrounded by a phi29-encoded, 174-base, RNA and a viral ATPase protein, both of which have fivefold symmetry in three-dimensional cryo-electron microscopy reconstructions. DNA is translocated into the prohead through a 36 A diameter pore in the center of the connector, where the DNA takes the role of a motor spindle. The helical nature of the DNA allows the rotational action of the connector to be transformed into a linear translation of the DNA. The crystal structure determination of connector crystals in space group C2 was initiated by molecular replacement, using an approximately 20 A resolution model derived from cryo-electron microscopy. The model phases were extended to 3.5 A resolution using 12-fold non-crystallographic symmetry averaging and solvent flattening. Although this electron density was not interpretable, the phases were adequate to locate the position of 24 mercury sites of a thimerosal heavy-atom derivative. The resultant 3.2 A single isomorphous replacement phases were improved using density modification, producing an interpretable electron-density map. The crystallographically refined structure was used as a molecular-replacement model to solve the structures of two other crystal forms of the connector molecule. One of these was in the same space group and almost isomorphous, whereas the other was in space group P2(1)2(1)2. The structural differences between the oligomeric connector molecules in the three crystal forms and between different monomers within each crystal show that the structure is relatively flexible, particularly in the protruding domain at the wide end of the connector. This domain probably acts as a bearing, allowing the connector to rotate within the pentagonal portal of the prohead during DNA packaging.

Friction of an elastomer sliding on polymeric model surfaces

We investigated experimentally the frictional behavior of compatible polymers sliding past each other at model interfaces of controlled molecular parameters. In particular, a crosslinked polydimethylsiloxane (PDMS) drop was moved on solid substrates coated with grafted or adsorbed PDMS “monolayers”. Several regimes exhibiting different dependences on sliding velocity have been observed. Systematic variation of the grafting density (Σ) of long connector molecules which tend to penetrate into the network yielded two opposing trends. At our lowest velocities, an increase of Σ resulted in higher friction, whereas at higher velocities, the same connectors led to a reduction of friction (lubrication effect!) with respect to a surface without connectors.

CDNA Cloning, mRNA Expression, and Chromosomal Mapping of Human and Mouse Periplakin Genes

A portion of the intracellular domain of Type XVII collagen, used as a bait in a yeast two-hybrid screen of an epidermal keratinocyte cDNA library, identified overlapping cDNA clones that showed a high degree of homology to envoplakin and other members of the plakin family of intermediate filament connector molecules. Subsequent cloning allowed identification of contiguous cDNA sequences with an open reading frame of 5268 bp encoding a putative polypeptide of 1756 amino acids with a computed molecular mass of 204.7 kDa. Northern analysis using these cDNA clones revealed a prominent band of ∼6.5 kb in keratinocytes, which was barely detectable in fibroblasts. Multiple tissue RNA analysis showed that this protein is highly expressed in tissues with a prominent component of epithelial cells. This novel member of the plakin family was designated periplakin. The human gene (PPL) was mapped to the interval between D16S510 and D16S509 by radiation hybrid mapping, corresponding to chromosomal band 16p13. Murine ESTs having 97.2% amino acid identity to the human sequence were identified. Interspecific backcross mapping was used to place the murine periplakin gene (Ppl) 0.53 cM distal to marker D16mit32 on the proximal part of murine chromosome 16, close to the locus of mahoganoid (md), a mouse hair mutant. Mapping of this gene in human and mouse will allow evaluation of periplakin as a candidate locus for disorders of epithelial fragility, with or without other phenotypes.

Crystal engineering: molecular networks based on inclusion phenomena

Inclusion processes based on molecular recognition processes may be used as a design principle for the generation of molecular networks in the solid state. Hollow tuneable molecular modules (koilands) based on fusion of preorganised cavities were shown to be assembled in the solid state into one-dimensional molecular arrays (koilates) either by self-inclusion or by interconnection using connector molecules. The formation of the molecular networks in the crystalline phase was established by X-ray studies.

Molecular tectonics: design, synthesis and structural analysis of a molecular network based on inclusion processes using a doubly fused p-isopropylcalix[4]arene

The synthesis of a hollow molecular module (koiland) possessing two divergent cavities was achieved by double fusion of two p-isopropylcalix[4]arenes in cone conformation by two silicon atoms. The formation of either a discrete binuclear inclusion complex in the presence of CH 2 Cl 2 acting as stopper or of an infinite 1-D inclusion network (koilate) in the presence of hexadiyne acting as connector was demonstrated in the solid state by single-crystal diffraction studies. The inclusion network was based on the interconnection of consecutive koilands by connector molecules.

Human keratin diseases: hereditary fragility of specific epithelial tissues.

Keratins are heteropolymeric proteins which form the intermediate filament cytoskeleton in epithelial cells. Since 1991, mutations in several keratin genes have been found to cause a variety of human diseases affecting the epidermis and other epithelial structures. Epidermolysis bullosa simplex (EBS) was the first mechanobullous disease for which the underlying genetic lesion was found, with mutations in both the K5 and K14 genes rendering basal epidermal keratinocytes less resilient to trauma, resulting in skin fragility. The site of mutation in the keratin protein correlates with phenotypic severity in this disorder. Since mutations were identified in the basal cell keratins, the total number of keratin genes associated with diseases has risen to eleven. The rod domains of suprabasal keratins K1 and K10 are mutated in bullous congenital ichthyosiform erythroderma (BCIE; also called epidermolytic hyperkeratosis, EH) and mosaicism for K1/K10 mutations results in a nevoid distribution of EH. An unusual mutation in the VI domain of K1 has also been found to cause diffuse non-epidermolytic palmoplantar keratoderma (DNEPPK). Mutations in palmoplantar specific keratin K9 cause epidermolytic palmoplantar keratoderma (EPPK) and mutations in the late differentiation suprabasal keratin K2e cause ichthyosis bullosa of Siemens (IBS). In the last year or so, mutations were discovered in differentiation specific keratins K6a and K16 causing pachyonychia congenita type 1 and K17 mutations occur in pachyonychia congenita type 2. K16 and K17 mutations have also been reported to produce phenotypes with little or no nail changes: K16 mutations can present as focal non-epidermolytic palmoplantar keratoderma (NEPPK) and K17 mutations can result in a phenotype resembling steatocystoma multiplex. Recently, mutation of mucosal keratin pair K4 and K13 has been shown to underlie white sponge nevus (WSN). This year, the first mutations in a keratin-associated protein, plectin, were shown to cause a variant of epidermolysis bullosa associated with late-onset muscular dystrophy (MD-EBS). An unusual mutation has been identified in K5 which is responsible for EBS with mottled pigmentation and genetic linkage analysis suggests that the hair disorder monilethrix is likely to be due to a mutation in a hair keratin. The study of keratin diseases has led to a better understanding of the importance of the intermediate filament cytoskeleton and associated connector molecules in maintaining the structural integrity of the epidermis and other high stress epithelial tissues, as well as allowing diagnosis at the molecular level thus facilitating prenatal testing for this heterogeneous group of genodermatoses.

Adhesion via connector molecules: the many-stitch problem

The fracture of adhesive junctions between two rubbers which are bound together by connectors, i.e., polymer chains which are chemically identical to the rubbers is studied. The one-stitch case in which each adhesive chain crosses the interface only once has been discussed previously. We focus here on the many-stitch case, in which each connector crosses the interface many times. A dynamical equation for fracture is derived. In the quasi-static limit, it is found that the fracture energy is not much larger than that in the one-stitch problem

Rubber-rubber adhesion with connector molecules

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTRubber-rubber adhesion with connector moleculesE. Raphael and P. G. De GennesCite this: J. Phys. Chem. 1992, 96, 10, 4002–4007Publication Date (Print):May 1, 1992Publication History Published online1 May 2002Published inissue 1 May 1992https://doi.org/10.1021/j100189a018RIGHTS & PERMISSIONSArticle Views786Altmetric-Citations190LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (496 KB) Get e-Alerts