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MATERIALS RESEARCH SCIENCE AND ENGINEERING CENTER

ABSTRACT:

 

Crystallization of L-cystine is a critical process in the pathogenesis of

kidney stone formation in cystinuria, a disorder affecting more than 20 000

individuals in the United States alone. In an effort to elucidate the crystallization of L-cystine and the mode of action of tailored growth inhibitors that may constitute effective therapies, real-time in situ atomic force microscopy has been used to investigate the surface micromorphology and growth kinetics of the {0001} faces of L-cystine at various supersaturations and concentrations of the growth inhibitor Lcystine dimethylester (CDME). Crystal growth is actuated by screw dislocations on the {0001} L-cystine surface, producing hexagonal spiral hillocks that are a consequence of six interlacing spirals of anisotropic molecular layers. The high level of elastic stress in the immediate vicinity around the dislocation line results in a decrease in the step velocities and a corresponding increase in the spacing of steps.

The kinetic curves acquired in the presence of CDME conform to the classical Cabrera−Vermilyea model. Anomalous birefringence in the {101̅0} growth sectors, combined with computational modeling, supports a high fidelity of stereospecific binding of CDME, in a unique orientation, exclusively at one of the six crystallographically unique projections on the {101̅0} plane.

A. G. Shtukenberg, L. N. Poloni, Z. Zhu, Z. An, M. Bhandari, P. Song, A. L. Rohl, Bart Kahr, M. D. Ward, Cryst. Growth Des. 2015, 15, 921

Overview:

Molecular-level insights into the use of L-cystine mimics (a.k.a. molecular imposters) for inhibition of L-cystine crystallization, a critical process in the pathogenesis of kidney stone formation in cystinuria, a disorder with no reliable therapy that affects more than 20,000 individuals in the United States

 

L-cystine crystals grow by synchronous motion of six-threaded interlaced spirals emanating from a dislocation core

 

Real-time atomic force microscopy and polarized light microscopy revealed the crystal growth mechanisms and mode of action of tailored growth inhibitors now being explored as therapeutic agent

 

Quantitative linear birefringence imaging revealed inclusion of tailored inhibitor molecules in symmetry-related sectors, with a remarkably high fidelity of stereospecific binding of the inhibitor, in a unique orientation, exclusively at one of six crystallographically unique molecular steps

 

Stereospecific binding corroborated by computational modeling

 

Thought experiment: Hard sphere glasses have many weak contacts. If we open several weak contacts (red), we induce flow along the purple arrows. Using the geometrical properties of these “soft modes” we show that many properties of the glass are strongly affected by the weak contacts. The thickness of the black lines scales with the amplitude of the contact forces between particles.