Department of Chemistry and the Molecular Design Institute, New York University, 100 Washington Square East, New York, New York 10003-6688, USA.
J Am Chem Soc. 2013 Apr 17;135(15):5525-8. doi: 10.1021/ja401309d. Epub 2013 Apr 4.
The pathogenesis of L-cystine kidney stones involves four critical steps: nucleation, crystal growth, crystal aggregation, and crystal adhesion to cells. Although inhibition of crystal growth by L-cystine "imposters" at L-cystine crystal surfaces has been suggested as a plausible route for the suppression of stones, understanding the factors that govern crystal-crystal aggregation and adhesion of crystals to epithelial cells also is essential for devising strategies to mitigate L-cystine stone formation. Chemical force microscopy performed with atomic force microscope tips decorated with functional groups commonly found in urinary constituents that likely mediate aggregation and attachment (e.g., COOH, NH2, SH, CH3, OH) revealed signatures that reflect differences in the chemical affinity of these groups for the (001) and {100} faces of the naturally occurring hexagonal form of L-cystine single crystals and the {110} faces of the non-native tetragonal form. These signatures can be explained by the different chemical compositions of the crystal faces, and they reveal a remarkable binding specificity of the thiol group for the sulfur-rich {100} and {110} faces of the hexagonal and tetragonal forms, respectively. Collectively, these observations suggest that alterations of the crystal habit and polymorph by crystal growth inhibitors may not affect crystal aggregation or adhesion to cells significantly.
L-胱氨酸肾结石的发病机制涉及四个关键步骤：成核、晶体生长、晶体聚集和晶体黏附到细胞。尽管在 L-胱氨酸晶体表面用 L-胱氨酸“仿制品”抑制晶体生长被认为是抑制结石形成的合理途径，但了解控制晶体-晶体聚集和晶体黏附到上皮细胞的因素对于制定减轻 L-胱氨酸结石形成的策略也至关重要。用原子力显微镜针尖上的功能基团进行化学力显微镜，这些功能基团通常存在于尿液成分中，可能介导聚集和附着（例如，COOH、NH2、SH、CH3、OH），揭示了反映这些基团对天然存在的 L-胱氨酸单晶的（001）和{100}面以及非天然四方形式的{110}面的化学亲和力差异的特征。这些特征可以用晶体面的不同化学成分来解释，它们分别揭示了巯基基团对富含硫的{100}和{110}面的惊人结合特异性，分别是六边形和四方形式。总之，这些观察结果表明，晶体生长抑制剂对晶体习性和多晶型的改变可能不会显著影响晶体聚集或黏附到细胞。
