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C A Orme

Publications and source records attributed to C A Orme.

5 recordsLinked to original sources
PubMed2006

Dual roles of brushite crystals in calcium oxalate crystallization provide physicochemical mechanisms underlying renal stone formation.

Calcium oxalate monohydrate (COM) crystals are the major mineral component of most kidney stones, and thus have an important role in chronic human disease. However, the physicochemical mechanisms leading to calcium oxalate (CaOx) stone disease are only partially defined. As spontaneous precipitation of CaOx is rare under renal conditions, an alternative pathway for CaOx crystallization seems necessary to resolve this central issue. We performed kinetic studies using the dual constant composition method to simultaneously analyze the crystallization of COM and brushite, the form of calcium phosphate that is most readily formed in the typical slightly acidic urinary milieu. These studies were supported by parallel analysis by scanning electron and atomic force microscopy. In these studies, mineralization of a thermodynamically stable phase (COM) was induced by the presence of brushite, a more readily precipitated inorganic phase. Furthermore, once formed, the COM crystals grew at the expense of brushite crystals causing the dissolution of the brushite crystals. These studies show that brushite may play crucial roles in the formation of COM crystals. The definition of these two roles for brushite thereby provides physicochemical explanations for the initiation of COM crystallization and also for the relative paucity of calcium phosphate detected in the majority of CaOx renal stones.

Calcium Oxalate↗
PubMed2004

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.

Calcium Oxalate↗
PubMed2001

Formation of chiral morphologies through selective binding of amino acids to calcite surface steps.

Many living organisms contain biominerals and composites with finely tuned properties, reflecting a remarkable level of control over the nucleation, growth and shape of the constituent crystals. Peptides and proteins play an important role in achieving this control. But the general view that organic molecules affect mineralization through stereochemical recognition, where geometrical and chemical constraints dictate their binding to a mineral, seems difficult to reconcile with a mechanistic understanding, where crystallization is controlled by thermodynamic and kinetic factors. Indeed, traditional crystal growth models emphasize the inhibiting effect of so-called 'modifiers' on surface-step growth, rather than stereochemical matching to newly expressed crystal facets. Here we report in situ atomic force microscope observations and molecular modelling studies of calcite growth in the presence of chiral amino acids that reconcile these two seemingly divergent views. We find that enantiomer-specific binding of the amino acids to those surface-step edges that offer the best geometric and chemical fit changes the step-edge free energies, which in turn results in macroscopic crystal shape modifications. Our results emphasize that the mechanism underlying crystal modification through organic molecules is best understood by considering both stereochemical recognition and the effects of binding on the interfacial energies of the growing crystal.

Amino Acids↗
PubMed2001

Mechanism of dissolution of sparingly soluble electrolytes.

Recent constant composition dissolution studies of sparingly soluble calcium phosphates have revealed an interesting and unusual behavior in that the rates decreased, eventually resulting in effective suppression, even though the solutions remained undersaturated. Contrary to traditional theories of dissolution, these experimental results indicated the importance of not only the particle size on the dissolution rate but also the participation of critical phenomena. In these theories, it is assumed that when the dissolution reactions are initiated, they continue spontaneously until all solid phase has disappeared. In terms of these mechanisms, there are no critical phenomena in the dissolution mechanism. Although the crystal size decreases during dissolution, when the reaction is controlled by polypitting (formation and growth of pits), the edge free energy increases at the very first stage due to the creation of pits and dissolution steps. The constant composition experimental results demonstrate the development of surface roughness as the dissolution steps are formed, implying an increase of the total edge length during the reactions. In an exactly analogous mechanism to crystal growth, the participation of critical conditions involving dissolution steps is a possibility. In contrast to crystal growth, dissolution is a process of size reduction and, when the particle size is sufficiently reduced, critical phenomena become important so that the influence of size must be taken into consideration. This paper proposes such a model for dissolution reactions, and although these unusual phenomena probably apply to all mineral phases, they are more evident for sparingly soluble electrolytes in which the critical conditions are attained much more readily.

Calcium Phosphates↗