Small Charged Molecule-Mediated\nFibrillar Mineralization:\nImplications for Ectopic Calcification

Numerous small biomolecules exist in the human body and\nplay roles\nin various biological and pathological processes. Small molecules\nare believed not to induce intrafibrillar mineralization alone. They\nare required to work in synergy with noncollagenous proteins (NCPs)\nand their analogs, <i>e.g</i>. polyelectrolytes, for inducing\nintrafibrillar mineralization, as the polymer-induced liquid-like\nprecursor (PILP) process has been well-documented. In this study,\nwe demonstrate that small charged molecules alone, such as sodium\ntripolyphosphate, sodium citrate, and (3-aminopropyl) triethoxysilane,\ncould directly mediate fibrillar mineralization. We propose that small\ncharged molecules might be immobilized in collagen fibrils to form\nthe polyelectrolyte-like collagen complex (PLCC) via hydrogen bonds.\nThe PLCC could attract CaP precursors along with calcium and phosphate\nions for inducing mineralization without any polyelectrolyte additives.\nThe small charged molecule-mediated mineralization process was evidenced\nby Cryo-TEM, AFM, SEM, FTIR, ICP-OES, <i>etc.</i>, as the\nPLCC exhibited both characteristic features of collagen fibrils and\npolyelectrolyte with increased charges, hydrophilicity, and density.\nThis might hint at one mechanism of pathological biomineralization,\nespecially for understanding the ectopic calcification process.