Understanding the Crystallization Pathway of Monosodium Urate Monohydrate in a Biomimetic Matrix

Gout is a kind of severe joint disease caused by monosodium urate monohydrate (MSUM) deposition in the synovial fluid. Numerous studies have focused on the influences of the components in synovial fluid on the nucleation of MSUM in solution. Yet little is known about the pathological pathway of MSUM crystallization in vivo. Herein, the pathological crystallization pathway of MSUM was investigated in a simulated biological environment (0.15 M Na+ and pH 7.40 buffer). Optical and electron microscope images in combination with powder X-ray diffraction demonstrated that the formation of MSUM involves three stages of molecular aggregation to form fibril-like amorphous subunits, the agglomeration of these nanosized subunits, and the phase transition from amorphous to filamentous crystals. Further, Fourier transform infrared spectroscopy and Raman spectra show that the filamentous crystals bear a structure extremely similar to that of amorphous agglomerates. However, the amorphous form contains more water content in comparison to that of MSUM crystals, as unveiled by thermal analyses. The time-resolved dynamic light scattering and small-angle X-ray scattering data reveal the formation of fibril-like nanoprecursors in the early stage of nucleation and the structure evolution over time. Thus, a nonclassical crystallization mechanism for MSUM in a simulated joint environment was proposed.