Biomimetic Coatings and Their Biological Functionalization

The biomimetic coating technique can be used to deposit layers of calcium phosphate (CaP) on medical devices to improve their osteoconductivity and osseointegration.The inorganic layer generated is akin to mineralized bone matrix and can be degraded as such. The biomimetic coating technique involves the nucleation and growth of bone-like crystals on a pretreated substrate by immersing it in a supersaturated solution of CaP under physiological conditions of temperature (37°C) and pH (7.4). The method, originally developed by Kokubo and his co-workers in 1990, has since undergone improvement and refinement by several groups of investigators. Biomimetic coatings are valuable in that they can serve as a vehicle for the slow, sustained release of osteogenic agents at the site of implantation. This attribute is rendered possible by the near-physiological conditions under which these coatings are prepared, which permits the incorporation of bioactive agents into the inorganic crystal latticework rather than their superficial adsorption on preformed layers. In addition, the biomimetic coating technique can be applied to implants of an organic as well as of a metallic nature and to those with irregular surface geometries, which is not possible using conventional methodologies.

Two-dimensional supramolecular polymers

One of the biggest issues of modern materials science is developing of strategies to create large and ordered assemblies in the form of discrete nanoscale objects. Oligopyrenotides (OPs) represent novel class of amphiphilic molecules which tend to self-assemble forming highly ordered structures. As has been already shown OPs are able to form 1D («rod-like») supramolecular polymer [1]. Since programmed arraying of polyaromatic hydrocarbons in structurally defined objects could offer enhanced performance over the individual components, prediction and controlling of their spatial arrangement remains challenging. Herein we demonstrate that certain changes to design of pyrene’s molecular core allow Py3 form 2D supramolecular assemblies («nanosheets») instead of 1D. Two dimensional supramolecular polymers are attractive objects due to their exceptional properties which originate from in-plan alignment of molecular units in the sheets with constant thickness ~ 2 nm [2]. These assemblies have high degree of internal order: the interior consists of hydrophobic pyrenes and alkyl chains, whereas the exterior exists as a net of hydrophilic, negatively charged phosphates. The Py3 units are hold up by non-covalent interactions what makes these assemblies totally reversible. Moreover the polymerization occurs via nucleation-elongation mechanism. To study Py3 self-assembly, we carried out whole set of spectroscopic (UV/vis, fluorescence, DLS) and microscopic experiments (AFM)

Two-dimensional supramolecular polymers

One of the biggest issues of modern materials science is developing of strategies to create large and ordered assemblies in the form of discrete nanoscale objects. Oligopyrenotides (OPs) represent novel class of amphiphilic molecules which tend to self-assemble forming highly ordered structures. As has been already shown OPs are able to form 1D («rod-like») supramolecular polymer [1]. Since programmed arraying of polyaromatic hydrocarbons in structurally defined objects could offer enhanced performance over the individual components, prediction and controlling of their spatial arrangement remains challenging. Herein we demonstrate that certain changes to design of pyrene’s molecular core allow Py3 form 2D supramolecular assemblies («nanosheets») instead of 1D. Two dimensional supramolecular polymers are attractive objects due to their exceptional properties which originate from in-plan alignment of molecular units in the sheets with constant thickness ~ 2 nm [2]. These assemblies have high degree of internal order: the interior consists of hydrophobic pyrenes and alkyl chains, whereas the exterior exists as a net of hydrophilic, negatively charged phosphates. The Py3 units are hold up by non-covalent interactions what makes these assemblies totally reversible. Moreover the polymerization occurs via nucleation-elongation mechanism. To study Py3 self-assembly, we carried out whole set of spectroscopic (UV/vis, fluorescence, DLS) and microscopic experiments (AFM)

Synthetic peptides corresponding to a repetitive sequence of malarial histidine rich protein bind haem and inhibit haemozoin formation in vitro

Synthetic peptides containing a repetitive hexapeptide sequence (Ala-His-His-Ala-Ala-Asp) of malarial histidine-rich protein II were evaluated for binding with haem in vitro. The pattern of haem binding suggested that each repeat unit of this sequence provides one binding site for haem. Chloroquine inhibited the haem-peptide complex formation with preferential formation of a haem chloroquine complex. In vitro studies on haem polymerisation showed that none of the peptides could initiate haemozoin formation. However, they could inhibit haemozoin formation promoted by a malarial parasite extract, possibly by competitively binding free haem. These results indicate this hexapeptide sequence represents the haem binding site of the malarial histidine-rich protein and possibly the site of nucleation for haem polymerisation.

Symmetry and the polar state of condensed molecular matter

Polar molecular crystals seem to contradict a quantum mechanical statement, according to which no stationary state of a system features a permanent electrical polarization. By stationary we understand here an ensemble for which thermal averaging applies. In the language of statistical mechanics we have thus to ask for the thermal expectation value of the polarization in molecular crystals. Nucleation aggregates and growing crystal surfaces can provide a single degree of freedom for polar molecules required to average the polarization. By means of group theoretical reasoning and Monte Carlo simulations we show that such systems thermalize into a bi-polar state featuring zero bulk polarity. A two domain, i.e. bipolar state is obtained because boundaries are setting up opposing effective electrical fields. Described phenomena can be understood as a process of partial ergodicity-restoring. Experimentally, a bi-polar state of molecular crystals was demonstrated using phase sensitive second harmonic generation and scanning pyroelectric microscopy

A FUNCTIONAL VARIANT OF HLA-DR1 DELINEATED BY T-LYMPHOCYTE CLONE REACTIVITY, PROTEIN CONFORMATION, AND GENOMIC RESTRICTION SITES

This research characterized a serologically indistinguishable form of HLA-DR1 that: (1) cannot stimulate some DR1-restricted or specific T-lymphocyte clones; (2) displays an unusual electrophoretic pattern on two dimensional gels; and (3) is marked by a polymorphic restriction site of the alpha gene. Inefficient stimulation of some DR1-restricted clones was a property of DR1$\sp{+}$ cells that shared HLA-B14 on the same haplotype and/or were carriers of 21-hydroxylase (21-OH) deficiency. Nonclassical 21-OH deficiency frequently demonstrates genetic linkage with HLA-B14;DR1 haplotypes and associates with duplications of C4B and one 21-OH gene. Cells having both stimulatory (DR1$\sb{\rm n}$) and nonstimulatory (DR1$\sb{\rm x}$) parental haplotypes did not mediate proliferation of these clones. However, heterozygous DR1$\sb{\rm x}$, 2 and DR1$\sb{\rm x}$, 7 cells were efficient stimulators of DR2 and DR7 specific clones, respectively, suggesting that a trans acting factor may modify DR1 alleles or products to yield a dominant DR1$\sb{\rm x}$ phenotype. Incompetent stimulator populations did not secrete an intercellular soluble or contact dependent suppressor factor nor did they express interleukin-2 receptors competing for T-cell growth factors. Two dimensional gel analysis of anti-DR immunoprecipitates revealed, in addition to normal DR$\alpha$ and DR$\beta$ chains, a 50kD species from DR1$\sb{\rm x}$ but not from the majority of DR1$\sb{\rm n}$ or non-DR1 cells. The 50kD structure was stable under reducing conditions in SDS and urea, had antigenic homology with DR, and dissociated after boiling into 34kD and 28kD peptide chains apparently identical with DR$\alpha$ and DR$\beta$ as shown by limited digest peptide maps. N-linked glycosylation and sialation of DRgp50 appeared to be unchanged from normal DR$\alpha$ and DR$\beta$. Bg1II digestion and $DR\alpha$ probing of DR1$\sb{\rm x}$ genomic DNA revealed a 4.5kb fragment while DR1$\sb{\rm n}$ DNA yielded 3.8 and 0.76kb fragments; all restriction sites mapped to the 3$\sp\prime$ untranslated region of $DR\alpha$. Collectively, these data suggest that DRgp50 represents a novel combinatorial association between constitutive chains of DR that may interfere with or compete for normal T cell receptor recognition of DR1 as both an alloantigen and restricting element. Furthermore, extensive chromosomal abnormalities previously mapped to the class III region of B14;DR1 haplotypes may extend into the adjacent class II region with consequent intrusion on immune function. ^

Diversity of morphological patterns in supramolecular polymers formed from the amphiphilic oligomers of pyrenes

Very important aspects of the modern nanotechnology are control and prediction of arraying patterns of opto- and electroactive molecules in discrete objects on nanoscale level both on surface and solution. Consequqntly, a self-assembly of small molucules provides such an opportunity.For example, oligopyrenotides (OPs, short amphiphilic pyrene oligomers) represent a novel class of amphiphilic molecules which tend to aggegate in aqueous phase. As has been already shown, OPs are able to form 1D supramolecular polymer only under high salt concentration. Since programmed arraying of polyaromatic hydrocarbons in structurally defined objects could offer enhanced performance over the individual components, prediction and controlling of their spatial arrangement remains challenging. Herein we demonstrate that substitution type of the pyrene is crutial, and it determines a morphology of the assemblies. Thus, a 1.6-linkage causes a formation of large, free-standing 2D supromolecular polymers with a thickness 2 nm. These assemblies possess a high degree of an internal order: the interior consists of hydrophobic pyrenes and alkyl chains, whereas the exterior exists as a net of hydrophilic negatively charged phosphates. Contrary, a 1.8-linkage exclusiveley leads to a formation of long (up to a few micrometer), nanometer thick helical supramolecular polymers. These structures tend to form even more complex structures (bundles, superhelixes). Moreover for both molecules, the polymerizations occurs via a nucleation-elongation mechanism. To study Py3 self-assembly, we carried out whole set of spectroscopic (UV/vis, fluorescence, DLS) and microscopic experiments (AFM).

Diversity of morphological patterns in supramolecular polymers formed from the amphiphilic oligomers of pyrenes

Herein we demonstrate that a substitution type of the pyrene in short amphiphilic oligomers determines a morphology of the assemblies formed. Thus, 1.6- and 2.7-linkages lead to a formation of micrometer-sized 2D supromolecular polymers with a constant thickness 2 nm (pictures A and B). These assemblies possess a high degree of an internal order: the interior consists of hydrophobic pyrenes and alkyl chains, whereas the exterior exists as a net of hydrophilic negatively charged phosphates. Contrary, a 1.8-linkage exclusiveley leads to a formation of long nanometer thick helical supramolecular polymers (picturee C). These structures tend to form even more complex assemblies (bundles, superhelixes). Moreover, for all samples the polymerization process occurs via a nucleation-elongation mechanism. To study Py3 self-assembly, we carried out whole set of spectroscopic (UV/vis, fluorescence, DLS) and microscopic experiments (AFM).

Microfabric memory of vein quartz for strain localization in detachment faults: A case study on the Simplon fault zone

This manuscript deals with the adaptation of quartz-microfabrics to changing physical deformation conditions, and discusses their preservation potential during subsequent retrograde deformation. Using microstructural analysis, a sequence of recrystallization processes in quartz, ranging from Grain-Boundary Migration Recrystallization (GBM) over Subgrain-Rotation Recrystallization (SGR) to Bulging Nucleation (BLG) is detected for the Simplon fault zone (SFZ) from the low strain rim towards the internal high strain part of the large-scale shear zone. Based on: (i) the retrograde cooling path; (ii) estimates of deformation temperatures; and (iii) spatial variation of dynamic recrystallization processes and different microstructural characteristics, continuous strain localization with decreasing temperature is inferred. In contrast to the recrystallization microstructures, crystallographic preferred orientations (CPO) have a longer memory. CPO patterns indicative of prism and rhomb glide systems in mylonitic quartz veins, overprinted at low temperatures (�400 �C), suggest inheritance of a high-temperature deformation. In this way, microstructural, textural and geochemical analyses provide information for several million years of the deformation history. The reasons for such incomplete resetting of the rock texture is that strain localization is caused by change in effective viscosity contrasts related to temporal large- and small-scale temperature changes during the evolution of such a long-lived shear zone. The spatially resolved, quantitative investigation of quartz microfabrics and associated recrystallization processes therefore provide great potential for an improved understanding of the geodynamics of large-scale shear zones.

Small quantity but large effect — How minor phases control strain localization in upper mantle shear zones

Low viscosity domains such as localized shear zones exert an important control on the geodynamics of the uppermost mantle. Grain size reduction and subsequent strain localization related to a switch from dislocation to diffusion creep is one mechanism to form low viscosity domains. To sustain strain localization, the grain size of mantle minerals needs to be kept small over geological timescales. One way to keep olivine grain sizes small is by pinning of mobile grain boundaries during grain growth by other minerals (second phases). Detailed microstructural studies based on natural samples from three shear zones formed at different geodynamic settings, allowed the derivation of the olivine grain-size dependence on the second-phase content. The polymineralic olivine grain-size evolution with increasing strain is similar in the three shear zones. If the second phases are to pin the mobile olivine grain boundary the phases need to be well mixed before grain growth. We suggest that melt-rock and metamorphic reactions are crucial for the initial phase mixing in mantle rocks. With ongoing deformation and increasing strain, grain boundary sliding combined with mass transfer processes and nucleation of grains promotes phase mixing resulting in fine-grained polymineralic mixtures that deform by diffusion creep. Strain localization due to the presence of volumetrically minor minerals in polymineralic mantle rocks is only important at high strain deformation (ultramylonites) at low temperatures (<~800°C). At smaller strain and stress conditions and/or higher temperatures other parameters like overall energy available to deform a given rock volume, the inheritance of mechanical anisotropies or the presence of water or melts needs to be considered to explain strain localization in the upper mantle.

Experimental study of electric breakdowns in liquid argon at centimeter scale

In this paper we present results on measurements of the dielectric strength of liquid argon near its boiling point and cathode-anode distances in the range of 0.1 mm to 40 mm with spherical cathode and plane anode. We show that at such distances the applied electric field at which breakdowns occur is as low as 40 kV/cm. Flash-overs across the ribbed dielectric of the high voltage feed-through are observed for a length of 300 mm starting from a voltage of 55 kV. These results contribute to set reference for the breakdown-free design of ionization detectors, such as Liquid Argon Time Projection Chambers (LAr TPC).

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Hierarchical self-assembly of the DNA-grafted supramolecular polymers

Conjugation of functional entities with a specific set of optical, mechanical or biological properties to DNA strands allows engineering of sophisticated DNA-containing architectures. Among various hybrid systems, DNA-grafted polymers occupy an important place in modern materials science. In this contribution we present the non-covalent synthesis and properties of DNA-grafted linear supramolecular polymers (SPs), which are assembled in a controllable manner from short chimeric DNA-pyrene oligomers. The synthetic oligomers consist of two parts: a 10 nucleotides long DNA chain and a covalently attached segment of variable number of phosphodiester-linked pyrenes. The temperature-dependent formation of DNA-grafted SPs is described by a nucleation-elongation mechanism. The high tendency of pyrenes to aggregate in water, leads to the rapid formation of SPs. The core of the assemblies consists of stacked pyrenes. They form a 1D platform, to which the DNA chains are attached. Combined spectroscopic and microscopic studies reveal that the major driving forces of the polymerization are π-stacking of pyrenes and hydrophobic interactions, and DNA pairing contributes to a lesser extent. AFM and TEM experiments demonstrate that the 1D SPs appear as elongated ribbons with a length of several hundred nanometers. They exhibit an apparent helical structure with a pitch-to-pitch distance of 50±15 nm. Since DNA pairing is a highly selective process, the ongoing studies are aimed to utilize DNA-grafted SPs for the programmable arrangement of functional entities. For example, the addition of non-modified complementary DNA strands to the DNA-grafted SPs leads to the cooperative formation of higher-order assemblies. Also, our experiments suggest that the fluorescent pyrene core of 1D ribbons serves as an efficient donor platform for energy transfer applications.

Granular flow in polymineralic rocks bearing sheet silicates: New evidence from natural examples

Natural deformation in carbonate mylonites bearing sheet silicates occurs via a complex interaction of granular flow and solution transfer processes and involves continuous cycles of dissolution, grain boundary diffusion, nucleation and growth. In this way, new sheet silicates (a) nucleate within voids formed by grain boundary sliding of calcite grains. (b) grow, and (c) rotate towards the shear plane. As a consequence, small mica grains show a wide range of orientations with respect to the shear plane, but moderate to large grains are subparallel both to each other and to the shear plane. Increases of average grain sizes with increasing temperature of sheet silicates in mica-rich layers is more pronounced than in mica-poor layers. In the calcitic matrix however, sheet silicates can only grow via solution-precipitation and mass transfer processes. Therefore, the observed grain size variability indicates drastic differences in mass transfer behavior between the individual layers, which might be related to differences in the fluid flux. Based on these observations, a conceptual model for the microfabric evolution in sheet silicate bearing mylonites is presented. © 2001 Elsevier Science B.V. All rights reserved.

Dissolution-Precipitation in Porous Media: Experiments and Modelling

The evolution of porosity due to dissolution/precipitation processes of minerals and the associated change of transport parameters are of major interest for natural geological environments and engineered underground structures. We designed a reproducible and fast to conduct 2D experiment, which is flexible enough to investigate several process couplings implemented in the numerical code OpenGeosys-GEM (OGS-GEM). We investigated advective-diffusive transport of solutes, effect of liquid phase density on advective transport, and kinetically controlled dissolution/precipitation reactions causing porosity changes. In addition, the system allowed to investigate the influence of microscopic (pore scale) processes on macroscopic (continuum scale) transport. A Plexiglas tank of dimension 10 × 10 cm was filled with a 1 cm thick reactive layer consisting of a bimodal grain size distribution of celestite (SrSO4) crystals, sandwiched between two layers of sand. A barium chloride solution was injected into the tank causing an asymmetric flow field to develop. As the barium chloride reached the celestite region, dissolution of celestite was initiated and barite precipitated. Due to the higher molar volume of barite, its precipitation caused a porosity decrease and thus also a decrease in the permeability of the porous medium. The change of flow in space and time was observed via injection of conservative tracers and analysis of effluents. In addition, an extensive post-mortem analysis of the reacted medium was conducted. We could successfully model the flow (with and without fluid density effects) and the transport of conservative tracers with a (continuum scale) reactive transport model. The prediction of the reactive experiments initially failed. Only the inclusion of information from post-mortem analysis gave a satisfactory match for the case where the flow field changed due to dissolution/precipitation reactions. We concentrated on the refinement of post-mortem analysis and the investigation of the dissolution/precipitation mechanisms at the pore scale. Our analytical techniques combined scanning electron microscopy (SEM) and synchrotron X-ray micro-diffraction/micro-fluorescence performed at the XAS beamline (Swiss Light Source). The newly formed phases include an epitaxial growth of barite micro-crystals on large celestite crystals (epitaxial growth) and a nano-crystalline barite phase (resulting from the dissolution of small celestite crystals) with residues of celestite crystals in the pore interstices. Classical nucleation theory, using well-established and estimated parameters describing barite precipitation, was applied to explain the mineralogical changes occurring in our system. Our pore scale investigation showed limits of the continuum scale reactive transport model. Although kinetic effects were implemented by fixing two distinct rates for the dissolution of large and small celestite crystals, instantaneous precipitation of barite was assumed as soon as oversaturation occurred. Precipitation kinetics, passivation of large celestite crystals and metastability of supersaturated solutions, i.e. the conditions under which nucleation cannot occur despite high supersaturation, were neglected. These results will be used to develop a pore scale model that describes precipitation and dissolution of crystals at the pore scale for various transport and chemical conditions. Pore scale modelling can be used to parameterize constitutive equations to introduce pore-scale corrections into macroscopic (continuum) reactive transport models. Microscopic understanding of the system is fundamental for modelling from the pore to the continuum scale.