Bioprocessing-Inspired Programmed Collagen Intrafibrillar Mineralization Controlled by Ligand Chain Length of Gold Nanoclusters
摘要
ABSTRACT Non-collagenous proteins (NCPs) critically regulate the precise integration of flexible collagen fibrils and rigid inorganic minerals in organisms. However, the ill-defined and low-contrast polymeric NCPs analogues obscure the corresponding molecular mechanisms. Here, electron-dense gold nanoclusters (AuNCs) functionalized with specific carboxyl ligands are proposed as the multi-functional NCPs analogues to both mediate and visualize the collagen mineralization process. Molecular dynamics simulation and in vitro mineralization results show that carboxyl ligands modified AuNCs can induce the formation of amorphous calcium phosphate (ACP) liquid precursors, but their stability and crystallization behavior strongly depend on ligand chain length-dependent interfacial properties. Interestingly, AuNCs with short-chain ligands stabilize the ACP liquid precursors, which infiltrate into the confined spaces of collagen fibrils in a ``gap-to-overlap’’ sequence, ultimately achieving co-localization with intrafibrillar minerals in overlap zones. Instead, AuNCs with long-chain ligands promote calcium phosphate crystallization, resulting in rapid extrafibrillar mineralization. Importantly, two distinct ACP liquid precursor types that participate in collage mineralization process via dissolution-reassembly interconversion are identified, in which particulate liquid precursors directly infiltrate collagen fibrils, while aggregated droplets serve as transient, dissolvable ion reservoirs. This study provides molecular insights into the biomineralization mechanism of collagenous tissues and a robust bioprocessing-inspired platform for designing next-generation repair materials.
