RESEARCH - Study of L-Cystine Crystal Growth and Inhibition via AFM

L-cystine stones are aggregates of individual crystals with hexagonal habits. The crystal structure (hexagonal P6122 space group, a = b = 0.5422 nm, c =5.6275 nm) reveals L-cystine molecules organized as a helix about the 61 screw axis so that six cystine molecules span the ~5.6-nm unit cell length of the c axis. The L-cystine molecules exhibit intermolecular NH3+…–O(C=O) hydrogen bonding along the 61 screw axis, intermolecular S…S interactions between the helices at intervals of c/2 along each of the six equivalent {100} directions, and NH3+…–O(C=O) hydrogen bonding between adjacent helices in the (001) plane. The hexagonal plate habit reflects the multiple strong intermolecular interactions in the (001) plane. From the atomic force microscopy AFM, we can observe different hexagonal hillocks on the (001) plane while the crystal is growing (Fig 1).


Crystallization of L-cystine is a critical step in the pathogenesis of cystine kidney stones. Treatments for this disease are somewhat effective but often lead to adverse side effects. Real-time in situ atomic force microscopy (AFM) reveals that L-cystine dimethylester (L-CDME) and L-cystine methylester (L-CME) dramatically reduce the growth velocity of the six symmetry-equivalent {100} steps because of specific binding at the crystal surface, which frustrates the attachment of L-cystine molecules. L-CDME and L-CME produce L-cystine crystals with different habits that reveal distinct binding modes at the crystal surfaces. The AFM observations are mirrored by reduced crystal yield and crystal size in the presence of L-CDME and L-CME, collectively suggesting a new pathway to the prevention of L-cystine stones by rational design of crystal growth inhibitors. Based on this, via Atomic Force Microscopy (AFM) and bulk crystallization, a library of different variations of L-cystine have been tested and compared.