Mice lacking the gene encoding matrix gla protein (MGP) exhibit massive mineral deposition in blood vessels and die soon after birth. We hypothesize that MGP prevents arterial calcification by adsorbing to growing hydroxyapatite (HA) crystals. To test this, we have used a combined experimental-computational approach. We synthesized peptides covering the entire sequence of human MGP, which contains three sites of serine phosphorylation and five sites of γ-carboxylation, and studied their effects on HA crystal growth using a constant-composition autotitration assay. In parallel studies, the interactions of these sequences with the {100} and {001} faces of HA were analyzed using atomistic molecular dynamics (MD) simulations. YGlapS (amino acids 1-14 of human MGP) and SK-Gla (MGP43-56) adsorbed rapidly to the {100} and {001} faces and strongly inhibited HA growth (IC(50) = 2.96 μg/mL and 4.96 μg/mL, respectively). QR-Gla (MGP29-42) adsorbed more slowly and was a moderate growth inhibitor, while the remaining three (nonpost-translationally modified) peptides had little or no effect in either analysis. Substitution of gla with glutamic acid reduced the adsorption and inhibition activities of SK-Gla and (to a lesser extent) QR-Gla but not YGlapS; substitution of phosphoserine with serine reduced the inhibitory potency of YGlapS. These studies suggest that MGP prevents arterial calcification by a direct interaction with HA crystals that involves both phosphate groups and gla residues of the protein. The strong correlation between simulated adsorption and measured growth inhibition indicates that MD provides a powerful tool to predict the effects of proteins and peptides on crystal formation. 相似文献
Kidney stones are crystal aggregates, most commonly containing calcium oxalate monohydrate (COM) microcrystals as the primary constituent. Macromolecules, specifically proteins rich with anionic side chains, are thought to play an important role in the regulation of COM growth, aggregation, and attachment to cells, all key processes in kidney stone formation. The microscopic events associated with crystal growth on the [010], [121], and [100] faces have been examined with in situ atomic force microscopy (AFM). Lattice images of each face reveal two-dimensional unit cells consistent with the COM crystal structure. Each face exhibits hillocks with step sites that can be assigned to specific crystal planes, enabling direct determination of growth rates along specific crystallographic directions. The rates of growth are found to depend on the degree of supersaturation of calcium oxalate in the growth medium, and the growth rates are very sensitive to the manner in which the growth solutions are prepared and introduced to the AFM cell. The addition of macromolecules with anionic side chains, specifically poly(acrylic acid), poly(aspartic acid), and poly(glutamic acid), results in inhibition of growth on the hillock step planes. The magnitude of this effect depends on the macromolecule structure, macromolecule concentration, and the identity of the step site. Poly(acrylic acid) was the most effective inhibitor of growth. Whereas poly(aspartic acid) inhibited growth on the (021) step planes of the (100) hillocks more than poly(glutamic acid), the opposite was found for the same step planes on the (010) hillocks. This suggests that growth inhibition is due to macromolecule binding to both planes of the step site or pinning of the steps due to binding to the (100) and (010) faces alone. The different profiles observed for these three macromolecules argue that local binding of anionic side chains to crystal surface sites governs growth inhibition rather than any secondary polymer structure. Growth inhibition by cationic macromolecules is negligible, further supporting an important role for proteins rich in anionic side chains in the regulation of kidney stone formation. 相似文献
Interactions of succinic acid (SUC) with the {104} cleavage faces of calcite show a strong preference in crystallographic directions. In situ atomic force microscopy revealed that the morphology of etch pits on the crystal surfaces experienced a transition from the common rhombus to a hexagon upon the introduction of SUC. The pit shape further evolved from 6-sided to 7-sided and eventually to 5-sided with increasing concentrations of SUC. Analysis indicates that the morphology changes may result from SUC preferentially binding to the [42] and [010] edges of the (104) plane to selectively slow down their step speed. 相似文献
Single crystals of cellulose triacetate II (CTA II) free of crystallization solvent can be grown from dilute solution in mixtures of dibenzyl ether and n-tetradecane. Good results are obtained by using a polymer fraction with a degree of polymerization of 60 and a mixture of 70% n-tetradecane and 30% dibenzyl ether at 245°C. The lamellar crystals produced are lozenge-shaped with the longer diagonal parallel to the a axis of the lattice and with {110} as the growth faces. Twin growth occurs frequently with {110} as a twinning plane and less frequently with {210}. 相似文献
Mineral-associated proteins have been proposed to regulate many aspects of biomineralization, including the location, type, orientation, shape, and texture of crystals. To understand how proteins achieve this exquisite level of control, we are studying the interaction between the phosphoprotein osteopontin (OPN) and the biomineral calcium oxalate monohydrate (COM). In the present study, we have synthesized peptides corresponding to amino acids 220-235 of rat bone OPN (pSHEpSTEQSDAIDpSAEK), one of several highly phosphorylated, aspartic-, and glutamic acid-rich sequences found in the protein. To investigate the role of phosphorylation in interaction with crystals, peptides containing no (P0), one (P1), or all three (P3) phosphates were prepared. Using a novel combination of confocal microscopy and scanning electron microscopy, we show that these peptides adsorb preferentially to {100} faces of COM and inhibit growth of these faces in a phosphorylation-dependent manner. To characterize the mechanism of adsorption of OPN peptides to COM, we have performed the first atomic-scale molecular-dynamics simulation of a protein-crystal interaction. P3 adsorbs to the {100} face much more rapidly than P1, which in turn adsorbs more rapidly than P0. In all cases, aspartic and glutamic acid, not phosphoserine, are the amino acids in closest contact with the crystal surface. These studies have identified a COM face-specific adsorption motif in OPN and delineated separate roles for carboxylate and phosphate groups in inhibition of crystal growth by mineral-associated phosphoproteins. We propose that the formation of close-range, stable, and face-specific interactions is a key factor in the ability of phosphoproteins to regulate biomineralization processes. 相似文献
The nucleation rate and propagation rate of steps on the {100} faces of polyethylene crystals have been determined. For single crystals, under conditions where the width of the {100} sectors remains constant during growth, it is confirmed that the growth is in regime I or the crossover region between regime I and II. In {110} twinned crystals, the {100} sectors are well developed and the width increases linearly with time; therefore, the growth in the twins must be in regime II. It is shown that the differing growth regimes of {100} faces in single crystals and twins allow the independent determination of the nucleation rate and the propagation rate of steps. The nucleation rate and propagation rate of steps on the {100} faces were determined from measurements of the constant width of the {100} faces in single crystals and the growth rate of the {100} faces in single crystals and twins. The observed rates show abnormal dependence on supercooling and concentration. The results are attributed to a weaker dependence of the constant width of {100} sectors on supercooling and concentration than predicted. 相似文献
Under near-physiological pH, temperature, and ionic strength, a kinetics constant composition (CC) method was used to examine the roles of phosphorylation of a 14 amino acid segment (DDVDDTDDSHQSDE) corresponding to potential crystal binding domains within the osteopontin (OPN) sequence. The phosphorylated 14-mer OPN peptide segment significantly inhibits both the nucleation and growth of calcium oxalate monohydrate (COM), inhibiting nucleation by markedly increasing induction times and delaying subsequent growth by at least 50% at concentrations less than 44 nM. Molecular modeling predicts that the doubly phosphorylated peptide binds much more strongly to both (-101) and (010) faces of COM. The estimated binding energies are, in part, consistent with the CC experimental observations. Circular dichroism spectroscopy indicates that phosphorylation does not result in conformational changes in the secondary peptide structure, suggesting that the local binding of negatively charged phosphate side chains to crystal faces controls growth inhibition. These in vitro results reveal that the interactions between phosphorylated peptide and COM crystal faces are predominantly electrostatic, further supporting the importance of macromolecules rich in anionic side chains in the inhibition of kidney stone formation. In addition, the phosphorylation-deficient form of this segment fails to inhibit COM crystal growth up to concentrations of 1450 nM. However, at sufficiently high concentrations, this nonphosphorylated segment promotes COM nucleation. Dynamic light scattering (DLS) and small-angle X-ray scattering (SAXS) results confirm that aggregation of the nonphosphorylated peptide segment takes place in solution above 900 nM when the aggregated peptide particles may exceed a well-defined minimum size to be effective crystallization promoters. 相似文献
The defect structure of organic materials is important as it plays a major role in their crystal growth properties. It also can play a subcritical role in “hot-spot” detonation processes of energetics and one such energetic is cyclotetramethylene-tetranitramine, in the commonly used beta form (β-HMX).
Results
The as-grown crystals grown by evaporation from acetone show prismatic, tabular and columnar habits, all with {011}, {110}, (010) and (101) faces. Etching on (010) surfaces revealed three different types of etch pits, two of which could be identified with either pure screw or pure edge dislocations, the third is shown to be an artifact of the twinning process that this material undergoes. Examination of the {011} and {110} surfaces show only one type of etch pit on each surface; however their natural asymmetry precludes the easy identification of their Burgers vector or dislocation type. Etching of cleaved {011} surfaces demonstrates that the etch pits can be associated with line dislocations. All dislocations appear randomly on the crystal surfaces and do not form alignments characteristic of mechanical deformation by dislocation slip.
Conclusions
Crystals of β-HMX grown from acetone show good morphological agreement with that predicted by modelling, with three distinct crystal habits observed depending upon the supersaturation of the growth solution. Prismatic habit was favoured at low supersaturation, while tabular and columnar crystals were predominant at higher super saturations. The twin plane in β-HMX was identified as a (101) reflection plane. The low plasticity of β-HMX is shown by the lack of etch pit alignments corresponding to mechanically induced dislocation arrays. On untwinned {010} faces, two types of dislocations exist, pure edge dislocations with b?=?[010] and pure screw dislocations with b?=?[010]. On twinned (010) faces, a third dislocation type exists and it is proposed that these pits are associated with pure screw dislocations with b?=?[010].
The direction of the polar axis of the potassium biphthalate (KAP) crystal was determined by anomalous X-ray scattering (λCu).
According to the etching pattern on the same sample, the positive direction of the axis corresponds to the slow-growing end
of the crystal. Crystal chemical features of the main faces of the KAP crystal ({111} and {111} pyramids, {010} pinacoid,
and {110} prism) were revealed. This allowed us to explain the anisotropy of impurity (ethylene glycol, di- or trivalent metal
cations) effects on the growth of separate faces of the crystal.
Institute of Crystallography, Russian Academy of Sciences. Translated fromZhurnal Struktumoi Khimii, Vol. 35, No. 5, pp. 143–148, September–October, 1994.
Translated by L. Smolina 相似文献
On the basis of Kirkendall Effect, high symmetric 18-facet polyhedral nanocrystals of Cu7S4 with a hollow nanocage could be converted from cubic nanocrystals of Cu2O in an aqueous media. The presence of organic additives makes the surface energy of {110} smaller than those of {100} and {111}. The growth of nanocrystals along the normal direction of highest energy surface {100} leads to the formation of a 18-facet polyhedron. 相似文献
The morphology of micrometer-sized beta-hematin crystals (synthetic malaria pigment) was determined by TEM images and diffraction, and by grazing incidence synchrotron X-ray diffraction at the air-water interface. The needle-like crystals are bounded by sharp {100} and {010} side faces, and capped by {011} and, to a lesser extent, by {001} end faces, in agreement with hemozoin (malaria pigment) crystals. The beta-hematin crystals grown in the presence of 10% chloroquine or quinine took appreciably longer to precipitate and tended to be symmetrically tapered toward both ends of the needle, due to stereoselective additive binding to {001} or {011} ledges. Evidence, but marginal, is presented that additives reduce crystal mosaic domain size along the needle axis, based on X-ray powder diffraction data. Coherent grazing exit X-ray diffraction suggests that the mosaic domains are smaller and less structurally stable than in pure crystals. IR-ATR and Raman spectra indicate molecular based differences due to a modification of surface and bulk propionic acid groups, following additive binding and a molecular rearrangement in the environment of the bulk sites poisoned by occluded quinoline. These results provided incentive to examine computationally whether hemozoin may be a target of antimalarial drugs diethylamino-alkoxyxanthones and artemisinin. A variation in activity of the former as a function of the alkoxy chain length is correlated with computed binding energy to {001} and {011} faces of beta-hematin. A model is proposed for artemisinin activity involving hemozoin nucleation inhibition via artemisinin-beta-hematin adducts bound to the principal crystal faces. Regarding nucleation of hemozoin inside the digestive vacuole of the malaria parasite, nucleation via the vacuole's membranous surface is proposed, based on a reported hemozoin alignment. As a test, a dibehenoyl-phosphatidylcholine monolayer transferred onto OTS-Si wafer nucleated far more beta-hematin crystals, albeit randomly oriented, than a reference OTS-Si. 相似文献
Despite the fragility of TiO(2) under electron irradiation, the intrinsic structure of Au/TiO(2) catalysts can be observed by environmental transmission electron microscopy. Under reaction conditions (CO/air 100?Pa), the major {111} and {100} facets of the gold nanoparticles are exposed and the particles display a polygonal interface with the TiO(2) support bounded by sharp edges parallel to the 〈110〉 directions. 相似文献
Eleven new 1-{5-[4-(benzyloxy)phenyl]-3-methyl-4,5-dihydropyrazol-l-yl} oxime ester dcrivatives were synthesized and characterized by elemental analysis, HRMS, ^1H NMR data. All the compounds were screened for their antibacterial potential in vitro against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. The results indicate that compounds 8c and 8f possess potent activity with the minimum inhibitory concentrations(MIC) of 1.562--3.125 ug/mL against all the four bacteria. Compounds 8c, 8e and 8f show moderate inhibition against the DNA gyrase(IC50=1.9--2.5 ug/mL). On the basis of the biological activities, structure-activity relationship was discussed. 相似文献
2-Chloro-N-{2-fluoro-5-[N-(phenylsulfonyl)phenylsulfonamido]phenyl}benzamide was synthesized and its crystal structure was also determined by X-ray single-crystal diffraction. The title compound(C25H18C1FN2O5S2) belongs to monoclinic, space group P21/n with a=0.7377(3) nm, b=1.2036(5) nm, c=2.6846(11) nm, β=90.895(9)°,V=2.3833(16) nm3, Mr=544.98, Z=4, Dc= 1.519 g/cm3, μ=0.385 mm-1, F(000)=1120, R1=0.0632, and wR2=0. 1438. Its crystal structure belongs to a novel class that has not been reported yet, and its preliminary herbicidal activity was also tested. Its inhibition rate to seedling growth of barnyard grass reaches 15.1% at 100 μg/mL. 相似文献
Atomic force microscopy has been used to image the various facets of two morphologically distinct samples of silicalite. The smaller (20 microm) sample A crystals show 1 nm high radial growth terraces. The larger (240 microm) sample B crystals show growth terraces 1 to 2 orders of magnitude higher than the terraces on sample A with growth edges parallel to the crystallographic axes. Moreover, the terraces on the (010) face are significantly higher than the terraces on the (100) face - inconsistent with the previously proposed 90 degrees intergrowth structure. Sample A highlights that under certain synthetic conditions, silicalite grows in a manner akin to zeolites Y and A, via the deposition of layers comprising, in the case of silicalite, pentasil chains. It is probable that the rate of terrace advance is identical on the (010) and (100) faces, and it is the rate of terrace nucleation that dictates the overall growth rate of each facet and hence the relative size expressed in the final crystal morphology. Analysis of the growth terraces of sample B and detailed consideration of the structures of both MFI, and a closely related material MEL, lead to the proposal of a generalized growth mechanism for silicalite including the incorporation of defects within the structure. These defects are thought to be responsible for both the relative and the absolute terrace heights observed and may also explain the hourglass phenomenon observed by optical microscopy. The implications of this growth mechanism, supported by results of infrared microscopy, generate a new dimension to the continuing debate on the existence of intergrowths within one of the most important structures relevant to zeolite catalysis. 相似文献