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Biomimetic synthesis of struvite with biogenic morphology and implication for pathological biomineralization.

Li H, Yao QZ, Wang YY, Li YL, Zhou GT - Sci Rep (2015)

Bottom Line: Recent studies have found that certain urinary proteins can efficiently inhibit stone formation.These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive.Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect.

View Article: PubMed Central - PubMed

Affiliation: CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026, P. R. China.

ABSTRACT
Recent studies have found that certain urinary proteins can efficiently inhibit stone formation. These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive. In the present study, polyaspartic acid (PASP) was employed as a model peptide to investigate the effect of urinary proteins on the crystallization and morphological evolution of struvite. The results demonstrate that selective adsorption/binding of PASP onto the {010} and {101} faces of struvite crystals results in arrowhead-shaped morphology, which further evolves into X-shaped and unusual tabular structures with time. Noticeably, these morphologies are reminiscent of biogenic struvite morphology. Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect. Considering that PASP is a structural and functional analogue of the subdomains of aspartic acid-rich proteins, our results reveal that aspartic acid-rich proteins play a key role in regulating biogenic struvite morphology, and aspartic acid residues contribute to the inhibitory capacity of urinary proteins. The potential implications of PASP for developing therapeutic agents for urinary stone disease is also discussed.

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FESEM image of the sample grown for 2 h in the presence of aspartic acid.
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f7: FESEM image of the sample grown for 2 h in the presence of aspartic acid.

Mentions: Moreover, our experiments using aspartic acid instead of PASP show that in the presence of aspartic acid, plenty of long irregular tabular struvite crystals (Figure 7) can be obtained (the XRD shown in Figure 1d). This shows that the aspartic acid monomer cannot exert a similar influence on the specific morphogenesis and growth inhibition of struvite as PASP in spite of the same stoichiometry of their respective carboxyl groups. Similar results have also been observed in the interactions between aspartic acid and other minerals, such as calcium hydrogenphosphate dihydrate and calcium oxalate monohydrate4651, indicating that a mass of carboxyl groups is insufficient to inhibit crystal growth and regulate the morphogenesis of struvite. It appears that the remarkable various effects can be attributed to the different molecule structures between PASP and aspartic acid. Using the circular dichroism technique, Addadi et al. confirmed that PASP with a molecular weight 6000 adopts a conformation comprising approximately 40% β-sheet and 60% random coil in Ca2+ solution61. The β-sheet conformation may favor the formation of more coordination bonds between PASP side chain carboxyl groups and magnesium cations exposed on the crystal face of struvite, and facilitate a structural and stereochemical fit between the distances of carboxylic groups in the PASP and the distances of neighboring magnesium cations from struvite crystal faces4648. In this way, PASP binds tightly with the crystal faces and regulates struvite morphogenesis. However, recent studies also demonstrated that many mineral-associated proteins lack periodic structures even when adsorbed to crystals626364, and thus Hunter et al. proposed a flexible polyelectrolyte hypothesis of protein-biomineral interaction64. In this model, protein-crystal interactions essentially involve a general electrostatic attraction rather than structural complementarities between the protein conformation and the crystal face. Therefore, the different mineralization effects between PASP and aspartic acid can also be reasonably interpreted as a high negative density and conformation flexibility of PASP relative to aspartic acid. At the same time, a mass of carboxyl groups allows for effective complexation between PASP and Mg2+ in solution, resulting in the growth inhibition of struvite. Therefore, comparative experiments with PASP and aspartic acid may highlight the importance of molecule conformation in morphogenesis and the growth inhibition of struvite. Based on these findings, it can safely be concluded that both the component (e.g., carboxylic functional group) and structure (chain length and molecule conformation) lead to the high inhibitory effectiveness of PASP. Furthermore, it should be kept in mind that PASP is a structural and functional analogue of aspartic acid residues in acidic proteins while aspartic acid residues are important components of some key urinary proteins intimately involved in the pathological mineralization processes of urinary stones18. For example, osteopontin contains approximately 15–20% aspartic acid residues24 and nephrocalcin contains approximately 11%51. Hence, we propose that aspartic acid residues or peptide chains in urinary proteins make an important contribution not only to the morphogenesis but also to the growth inhibition of the struvite stones.


Biomimetic synthesis of struvite with biogenic morphology and implication for pathological biomineralization.

Li H, Yao QZ, Wang YY, Li YL, Zhou GT - Sci Rep (2015)

FESEM image of the sample grown for 2 h in the presence of aspartic acid.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4296295&req=5

f7: FESEM image of the sample grown for 2 h in the presence of aspartic acid.
Mentions: Moreover, our experiments using aspartic acid instead of PASP show that in the presence of aspartic acid, plenty of long irregular tabular struvite crystals (Figure 7) can be obtained (the XRD shown in Figure 1d). This shows that the aspartic acid monomer cannot exert a similar influence on the specific morphogenesis and growth inhibition of struvite as PASP in spite of the same stoichiometry of their respective carboxyl groups. Similar results have also been observed in the interactions between aspartic acid and other minerals, such as calcium hydrogenphosphate dihydrate and calcium oxalate monohydrate4651, indicating that a mass of carboxyl groups is insufficient to inhibit crystal growth and regulate the morphogenesis of struvite. It appears that the remarkable various effects can be attributed to the different molecule structures between PASP and aspartic acid. Using the circular dichroism technique, Addadi et al. confirmed that PASP with a molecular weight 6000 adopts a conformation comprising approximately 40% β-sheet and 60% random coil in Ca2+ solution61. The β-sheet conformation may favor the formation of more coordination bonds between PASP side chain carboxyl groups and magnesium cations exposed on the crystal face of struvite, and facilitate a structural and stereochemical fit between the distances of carboxylic groups in the PASP and the distances of neighboring magnesium cations from struvite crystal faces4648. In this way, PASP binds tightly with the crystal faces and regulates struvite morphogenesis. However, recent studies also demonstrated that many mineral-associated proteins lack periodic structures even when adsorbed to crystals626364, and thus Hunter et al. proposed a flexible polyelectrolyte hypothesis of protein-biomineral interaction64. In this model, protein-crystal interactions essentially involve a general electrostatic attraction rather than structural complementarities between the protein conformation and the crystal face. Therefore, the different mineralization effects between PASP and aspartic acid can also be reasonably interpreted as a high negative density and conformation flexibility of PASP relative to aspartic acid. At the same time, a mass of carboxyl groups allows for effective complexation between PASP and Mg2+ in solution, resulting in the growth inhibition of struvite. Therefore, comparative experiments with PASP and aspartic acid may highlight the importance of molecule conformation in morphogenesis and the growth inhibition of struvite. Based on these findings, it can safely be concluded that both the component (e.g., carboxylic functional group) and structure (chain length and molecule conformation) lead to the high inhibitory effectiveness of PASP. Furthermore, it should be kept in mind that PASP is a structural and functional analogue of aspartic acid residues in acidic proteins while aspartic acid residues are important components of some key urinary proteins intimately involved in the pathological mineralization processes of urinary stones18. For example, osteopontin contains approximately 15–20% aspartic acid residues24 and nephrocalcin contains approximately 11%51. Hence, we propose that aspartic acid residues or peptide chains in urinary proteins make an important contribution not only to the morphogenesis but also to the growth inhibition of the struvite stones.

Bottom Line: Recent studies have found that certain urinary proteins can efficiently inhibit stone formation.These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive.Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect.

View Article: PubMed Central - PubMed

Affiliation: CAS Key Laboratory of Crust-Mantle Materials and Environments, School of Earth and Space Sciences, University of Science and Technology of China, Hefei 230026, P. R. China.

ABSTRACT
Recent studies have found that certain urinary proteins can efficiently inhibit stone formation. These discoveries are significant for developing effective therapies for stone disease, but the inhibition mechanism of crystallization remains elusive. In the present study, polyaspartic acid (PASP) was employed as a model peptide to investigate the effect of urinary proteins on the crystallization and morphological evolution of struvite. The results demonstrate that selective adsorption/binding of PASP onto the {010} and {101} faces of struvite crystals results in arrowhead-shaped morphology, which further evolves into X-shaped and unusual tabular structures with time. Noticeably, these morphologies are reminiscent of biogenic struvite morphology. Concentration-dependent experiments show that PASP can inhibit struvite growth and the inhibitory capacity increases with increasing PASP concentration, whereas aspartic acid monomers do not show a significant effect. Considering that PASP is a structural and functional analogue of the subdomains of aspartic acid-rich proteins, our results reveal that aspartic acid-rich proteins play a key role in regulating biogenic struvite morphology, and aspartic acid residues contribute to the inhibitory capacity of urinary proteins. The potential implications of PASP for developing therapeutic agents for urinary stone disease is also discussed.

Show MeSH
Related in: MedlinePlus