Effect of Urinary Macromolecules on l -Cystine Crystal Growth and Crystal Surface Adhesion

l-Cystine is the primary crystalline component of l-cystine kidney stones, which are a consequence of cystinuria, a genetic disorder that results from mutation in the SLC3A1 or the SLC7A9 gene. Urinary macromolecules present in the cellular matrix are thought to play a role in the pathogenesis of kidney stones affecting crystal nucleation, growth, crystal-crystal aggregation, and adhesion to epithelial cells. The effect of six prevalent urinary constituents - osteopontin, Tamm-Horsfall protein, albumin, apotransferrin, chondroitin sulfate, and lysozyme - on crystallization kinetics and adhesion events on the l-cystine (0001) surface was investigated with real-time in situ atomic force microscopy (AFM). These additives did not significantly change crystal morphology and crystallization yield, although slight reductions in step velocities were observed at nanogram per milliliter and microgram per milliliter concentrations. Chemical force microscopy performed with AFM tips decorated with terminal carboxylate, amino, and cysteine moieties revealed that macromolecular additives reduce the binding affinity of the {0001} face of l-cystine toward these groups. Collectively, these observations suggest that these macromolecules may actually mitigate l-cystine crystal growth and aggregation into stones.