Time-Resolved Dynamics\nof Calcium Oxalate Dihydrate\nCrystallization

Calcium oxalate is a common biomineral that forms in\nplants and\nhumans. The deleterious effects associated with the pathological crystallization\nof calcium oxalate in diseases such as kidney stones and breast cancer\ndepend upon the structural form of the crystal. The majority of studies\nin the literature focus on understanding and controlling the formation\nof calcium oxalate monohydrate (COM), which is the most prevalent\nform <i>in vivo</i>. Relatively fewer studies have examined\nthe crystallization of calcium oxalate dihydrate (COD), which is a\nless thermodynamically stable hydrate and the focus of this study.\nHere, we investigate methods of preparing large COD crystals using\npoly(acrylic acid) as a growth modifier to promote dihydrate nucleation\nand to generate crystals with a size and morphology that allow for <i>in situ</i> measurements of crystallization in physiologically\nrelevant growth media. Time-resolved dynamics of COD surface growth\nwere tracked in supersaturated calcium oxalate solutions using atomic\nforce microscopy (AFM) to visualize the birth and spreading of unfinished\nlayers on COD {100} crystal surfaces in real time. Our findings reveal\nthat COD growth involves the nucleation and advancement of two-dimensional\nislands, which is in stark contrast to COM surfaces that grow exclusively\nfrom screw dislocations. AFM studies performed over a range of supersaturation\nindicate that COD grows at a significantly slower rate with a kinetic\ncoefficient that is more than an order of magnitude smaller than that\nof COM. Similar <i>in situ</i> experiments were performed\nin the presence of citrate, a known inhibitor of calcium oxalate crystallization.\nThese studies reveal distinct differences in the impact of citrate\non COM and COD growth, which may have implications for its efficacy\nas an administered preventative therapeutic for pathological crystallization.