J. J. De Yoreo

Molecular modulation of calcium oxalate crystallization by osteopontin and citrate

Calcium oxalate monohydrate (COM), which plays a functional role in plant physiology, is a source of chronic human disease, forming the major inorganic component of kidney stones. Understanding molecular mechanisms of biological control over COM crystallization is central to development of effective stone disease therapies and can help define general strategies for synthesizing biologically inspired materials. To date, research on COM modification by proteins and small molecules has not resolved the molecular-scale control mechanisms. Moreover, because proteins directing COM inhibition have been identified and sequenced, they provide a basis for general physiochemical investigations of biomineralization. Here, we report molecular-scale views of COM modulation by two urinary constituents, the protein osteopontin and citrate, a common therapeutic agent. Combining force microscopy with molecular modeling, we show that each controls growth habit and kinetics by pinning step motion on different faces through specific interactions in which both size and structure determine the effectiveness. Moreover, the results suggest potential for additive effects of simultaneous action by both modifiers to inhibit the overall growth of the crystal and demonstrate the utility of combining molecular imaging and modeling tools for understanding events underlying aberrant crystallization in disease.

Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth

The composition of biologic molecules isolated from biominerals suggests that control of mineral growth is linked to biochemical features. Here, we define a systematic relationship between the ability of biomolecules in solution to promote the growth of calcite (CaCO3) and their net negative molecular charge and hydrophilicity. The degree of enhancement depends on peptide composition, but not on peptide sequence. Data analysis shows that this rate enhancement arises from an increase in the kinetic coefficient. We interpret the mechanism of growth enhancement to be a catalytic process whereby biomolecules reduce the magnitude of the diffusive barrier, Ek, by perturbations that displace water molecules. The result is a decrease in the energy barrier for attachment of solutes to the solid phase. This previously unrecognized relationship also rationalizes recently reported data showing acceleration of calcite growth rates over rates measured in the pure system by nanomolar levels of abalone nacre proteins. These findings show that the growth-modifying properties of small model peptides may be scaled up to analyze mineralization processes that are mediated by more complex proteins. We suggest that enhancement of calcite growth may now be estimated a priori from the composition of peptide sequences and the calculated values of hydrophilicity and net molecular charge. This insight may contribute to an improved understanding of diverse systems of biomineralization and design of new synthetic growth modulators.

Rapid growth of large-scale (40–55 cm) KH2PO4 crystals

KDP (KH2PO4) single crystals up to 45 cm in size have been grown by the rapid growth technique on the point seed in glass crystallizers of 1000 L in volume at growth rates of 10–20 mm/day in both the [0 0 1] and [1 0 0] directions.

An in-situ AFM investigation of canavalin crystallization kinetics

We present the results of an in-situ atomic force microscopy investigation of the kinetics of canavalin crystal growth. The results show that, depending on the supersaturation, growth occurs on steps of one growth unit in height generated either by simple and complex screw dislocation sources, 2D nucleating islands, or macroclusters which sediment onto the surface before spreading laterally as step bunches. The step velocity of canavalin at three different pHs (pH = 7.0, 7.7 and 8.0) varies linearly with concentration and gives a kinetic coefficient β which depends strongly on pH, with β ≈ 2.6 × 10−3 cm s−1 at pH 7.3 to β ≈ 5.8 × 10−4 cm s−1 at pH 8.0. Analysis of the velocity of single steps versus that of step bunches created by macroclusters, as well as the occurrence of 2D nucleation on broad terraces, constrains the length scale for diffusion to be of the order of 1 mm. A simple diffusion analysis is presented which indicates that surface diffusion rather than bulk diffusion is the controlling mechanism of solute transport to the steps. A demonstration of step homogenization with an exponential time dependence for step pair decay is presented, and is found to be in qualitative agreement with predictions of the models of Schwoebel and Shipsey and Ehrlich and Hudda [R.L. Schwoebel. E.J. Shipsey, J. Appl. Phys. 37 (1966) 3682; G. Ehrlich, F.G. Hudda, J. Chem. Phys. 44 (1966) 1039]. showing that the behavior of the system is consistent with a model of surface-diffusion controlled growth coupled with an up-step diffusion bias. The relationship between step speed and terrace width during step homogenization was investigated quantitatively using the model of Gilmer et al. [G.H. Gilmer, R. Ghez, N. Cabrera, J. Crystal Growth 8 (1971) 79]. The best fit to the data is obtained with a surface diffusion length of 0.4–0.9 μm, and leads to estimates for values of the activation energy for adsorption to the terrace Ead, and for incorporation at the step Einc, of 0.27 and <0.1 eV, respectively. The results of this analysis are compared to those obtained from interferometric measurements on NH4H2PO4 (ADP), a common inorganic crystal, for which the kinetic coefficient is three orders of magnitude larger. The comparison indicates that the main reason for this difference is the slow adsorption rate to the surface for canavalin as compared to ADP.

The effect of dislocation cores on growth hillock vicinality and normal growth rates of KDP {1 0 1} surfaces

We present results from atomic force microscopy measurements on KDP {1 0 1} faces which show that over the range of supersaturations, 3% ≤ σ ≤ 30%, the terrace widths on vicinal growth hillocks formed by dislocations are nearly independent of both supersaturation and dislocation structure, in contradiction to the predictions of simple BCF models. The data also show that, for Burgers vectors in excess of one unit step height, the dislocations generate hollow cores in accordance with theoretical predictions. Both analytical and numerical analyses are presented, which show that a model that takes into account the effect of these cores on the period of step rotation predicts a dependence of slope on supersaturation and Burgers vector, which is in good agreement with the experimental results. These calculations also show that the effect of the core perimeter on the step transit time dominates the effect of reduced step velocity due to stresses near the core. Consequently, a simple analytical expression can be used to describe the slope even in the case of anistropic step kinetics. Finally, the results are used to explain the reproducible character of macroscopic growth rates and to rescale data on growth rate as a function of temperature and supersturation onto a single curve.

X-ray diffraction studies of potassium dihydrogen phosphate (KDP) crystal surfaces

We have studied the surface atomic structure of KDP crystals using X-ray scattering. These crystals were grown from an aqueous solution and we have done measurements both ex situ and in situ. The ex situ measurements were performed in vacuum or in air. In order to be able to do in situ measurements, we designed and built a crystal growth chamber which is compatible with X-ray diffraction experiments. The atomic arrangement of the two naturally existing faces of KDP has been determined. Preliminary results are presented of measurements performed during growth. Furthermore, the influence of metal impurities on the atomic structure of the growing interface is examined.

Subnanometer atomic force microscopy of peptide-mineral interactions links clustering and competition to acceleration and catastrophe.

In vitro observations have revealed major effects on the structure, growth, and composition of biomineral phases, including stabilization of amorphous precursors, acceleration and inhibition of kinetics, and alteration of impurity signatures. However, deciphering the mechanistic sources of these effects has been problematic due to a lack of tools to resolve molecular structures on mineral surfaces during growth. Here we report atomic force microscopy investigations using a system designed to maximize resolution while minimizing contact force. By imaging the growth of calcium-oxalate monohydrate under the influence of aspartic-rich peptides at single-molecule resolution, we reveal how the unique interactions of polypeptides with mineral surfaces lead to acceleration, inhibition, and switching of growth between two distinct states. Interaction with the positively charged face of calcium-oxalate monohydrate leads to formation of a peptide film, but the slow adsorption kinetics and gradual relaxation to a well-bound state result in time-dependent effects. These include a positive feedback between peptide adsorption and step inhibition described by a mathematical catastrophe that results in growth hysteresis, characterized by rapid switching from fast to near-zero growth rates for very small reductions in supersaturation. Interactions with the negatively charged face result in formation of peptide clusters that impede step advancement. The result is a competition between accelerated solute attachment and inhibition due to blocking of the steps by the clusters. The findings have implications for control of pathological mineralization and suggest artificial strategies for directing crystallization.

Sources of optical distortion in rapidly grown crystals of KH2PO4

Abstract We report the results of X-ray topographic and optical measurements on KH 2 PO 4 crystals grown at rates of 5–30 mm/day. We show that optical distortion in these crystals is caused primarily by three sources: dislocations, differences in composition between adjacent growth sectors of the crystal, and differences in composition between adjacent sectors of vicinal-growth hillocks within a single growth sector of the crystal. We find that the compositional heterogeneities cause spatial variations in the refractive index and induce a distortion of the transmitted-wave front, while large groups of dislocations are responsible for strain-induced birefringence which leads to beam depolarization.

Raman scattering investigation of KH2PO4 subsequent to high fluence laser irradiation

The spectral characteristics of the internal (PO4 tetrahedron) modes of fast-grown KH2PO4 crystals under sub-damage threshold, 10 ns, 355 nm laser irradiation have been investigated. Pump-and-probe Raman spectroscopy indicates transient changes of the intensity of the 915 cm−1, –PO4 internal mode. This change is attributed to a transient increase of the absorption due to generation by the 355 nm pump pulse of electronic defects in the bulk of the crystal.

In situ atomic force microscopy of layer-by-layer crystal growth and key growth concepts

Contradictions that have been found recently between the representations of classical theory and experiments on crystal growth from solutions are considered. Experimental data show that the density of kinks is low in many cases as a result of the low rate of their fluctuation generation, the Gibbs-Thomson law is not always applicable in these cases, and there is inconsistency with the Cabrera-Vermilyea model. The theory of growth of non-Kossel crystals, which is to be developed, is illustrated by the analysis of the experimental dependence of the growth rate on the solution stoichiometry.