Journal Article

Bio-inspired multifunctional disruptors of calcium oxalate crystallization

Fisher, Saxton D., Alamani, Bryan G., Chauhan, Vraj P., Rimer, Jeffrey D., Jones, Matthew R., Vekilov, Peter G., Terlier, Tanguy, Kim, Doyoung, Yang, Zhi

2025

Overview

Calcium mineralization in biological and geological systems is often regulated by (macro)molecules enriched with anionic functional moieties. Relatively few studies have examined the effects of phosphate-based modifiers that are integral in calcification underlying human bone formation and pathological diseases. Here we mimic posttranslational phosphorylated moieties of a biologically-active inhibitor protein and demonstrate that polyphosphates and phosphonates suppress calcium oxalate nucleation, tailor solvate crystal structure, and irreversibly inhibit crystal growth in ways that significantly deviate from commonly investigated carboxylate-rich modulators of biomineralization. The most potent modifiers exhibit an uncommon dual mode of action, wherein nucleation is suppressed by altering prenucleation clusters and crystal surface growth is impeded irreversibly by inducing lattice strain. Once crystal surfaces are exposed to modifiers, recrystallization is severely restricted. This exemplifies the uniqueness and efficiency of phosphates wherein their multiple modes of action are promising characteristics for designing de novo biologically-inspired molecules as mineralization regulators. Control of crystallisation is important in biogenic and pathological biomineralisation. Here, the authors report on phosphorylated molecules that mimic proteins which can suppress calcium oxalate nucleation and irreversibly inhibit crystal growth in ways that significantly deviate from commonly investigated carboxylate-rich modulators of biomineralization.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 142/136 / 147/135 / 147/143 / 639/166/898 / 639/301/54 / 639/301/54/991 / Biomineralization / Bone growth / Calcification / Calcium / Calcium oxalate / Calcium Oxalate - chemistry / Calcium Oxalate - metabolism / Crystal growth / Crystal lattices / Crystal structure / Crystal surfaces / Crystallization / Humanities and Social Sciences / Humans / Lattice strain / Lattice vibration / Mineralization / Mode of action / multidisciplinary / Nucleation / Organophosphonates - chemistry / Organophosphonates - pharmacology / Osteogenesis / Oxalic acid / Phosphates / Phosphates - chemistry / Phosphonates / Polyphosphates / Proteins / Recrystallization / Science / Science (multidisciplinary)