| Calcium oxalate monohydrate (COM, whewellite, CaC2O4 ·H2O) is the most thermodynamically stable phase of calcium oxalate and is the primary mineral phase of human kidney stones. Although normal urine is often supersaturated with respect to calcium oxalate, less than 15% of the U.S. population suffers from stone formation; naturally occurring biomolecules are believed to prevent stone formation in the majority of the population.;A characteristic shared by many macromolecules implicated in urolithiasis is the presence of domains rich in aspartic acid, and more generally, the presence of multiple carboxylate functional groups. The effects of citrate, Tamm-Horsfall protein, and linear aspartic-acid-rich peptides are found to be highly face-specific. Growth of the (-101) face of COM is inhibited by citrate and the aspartic-acid-rich peptides; however, growth of the (010) face is both inhibited and promoted by Tamm-Horsfall protein and the aspartic-acid-rich peptides, depending on solution composition. With some modification, the step-pinning model of Cabrera and Vermilyea correctly predicts step kinetics in the presence of citrate and aspartic acid-rich peptides on the (-101) face, and a mechanism is proposed to explain the acceleration observed on the (010) face. The bifunctional effects of aspartic-acid-rich molecules on the (010) face, for which a mechanism is proposed, have broad implications for biomineralization.;Although a number of small molecules and ions (e.g. citrate and magnesium) and proteins (e.g. osteopontin and Tamm-Horsfall protein) have been implicated in stone formation, in many cases their exact roles in urolithiasis remain undefined. Furthermore, even in cases where the role is known, the underlying mechanisms remain a mystery. Not only do published reports often conflict, their results are frequently based on studies of bulk crystallization, which cannot directly observe the relevant processes at the near-molecular level. The work presented in this dissertation is based on in situ atomic-force microscopy (AFM) studies that measure changes in COM morphology and step kinetics at the near-molecular level. |
