Kim Doyoung, Chauhan Vraj P, Alamani Bryan G, Fisher Saxton D, Yang Zhi, Jones Matthew R, Terlier Tanguy, Vekilov Peter G, Rimer Jeffrey D
William A. Brookshire Department of Chemical and Biomolecular Engineering, University of Houston, 4226 Martin Luther King Blvd., Houston, TX, 77204-4004, USA.
Welch Center for Advanced Bioactive Materials Crystallization, University of Houston, 4226 Martin Luther King Blvd, Houston, TX, 77204-4004, USA.
Nat Commun. 2025 Jun 5;16(1):5229. doi: 10.1038/s41467-025-60320-4.
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.
生物和地质系统中的钙矿化通常受富含阴离子功能基团的（大）分子调控。相对较少的研究考察了基于磷酸盐的改性剂在人类骨骼形成和病理疾病相关钙化过程中的作用。在此，我们模拟了一种生物活性抑制蛋白的翻译后磷酸化部分，并证明多磷酸盐和膦酸盐能抑制草酸钙成核、调整溶剂化物晶体结构，并以显著不同于常见的富含羧酸盐的生物矿化调节剂的方式不可逆地抑制晶体生长。最有效的改性剂表现出一种罕见的双重作用模式，即成核通过改变预成核簇而受到抑制，晶体表面生长则通过诱导晶格应变而被不可逆地阻碍。一旦晶体表面暴露于改性剂，再结晶就会受到严重限制。这体现了磷酸盐的独特性和有效性，其多种作用模式是设计新型生物启发分子作为矿化调节剂的有前景的特性。
