Bio-inspired multifunctional disruptors of calcium oxalate crystallization

Abstract 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...

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Main Authors: Doyoung Kim, Vraj P. Chauhan, Bryan G. Alamani, Saxton D. Fisher, Zhi Yang, Matthew R. Jones, Tanguy Terlier, Peter G. Vekilov, Jeffrey D. Rimer
Format: Article
Language:English
Published: Nature Portfolio 2025-06-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-025-60320-4
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Summary:Abstract 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.
ISSN:2041-1723