Effect of Chondroitin 4-Sulfate on the Growth and Morphology of Calcium Oxalate Monohydrate: A Molecular Dynamics Study

Abstract

Classical Molecular Dynamics (MD) simulations were used to study the interaction of a dimer of chondroitin 4-sulfate (Ch4S) with the (100), (010), and (121) surfaces of the mineral calcium oxalate monohydrate (COM). The Ch4S glycosaminoglycan has been implicated in the modulation of the biomineralization process of kidney stones. MD simulations of the mineral surfaces and the disaccharide in the presence of solvent water allowed us to compute the adsorption energies of the saccharides on the COM surfaces. The calculations show that Ch4S interacts with COM principally through the sulfate, the carboxylate and the carbonyl of the acetyl amine functional groups. The mode and strength of the interaction depends on the orientation of the disaccharide with respect to the surface and the ability of the Ch4S to replace the interactions of the water molecules that compete with the saccharide for adsorption sites on the COM surface. Ch4S binds more strongly to the (010) than the (100) surface, leading to a more pronounced [001]/[010] aspect ratio in the calculated crystal morphology.

In Vitro Studies Reveal Antiurolithic Effect of Antioxidant Sulfated Polysaccharides from the Green Seaweed Caulerpa cupressoides var flabellata

“…However, there are no studies that prove direct binding between SPs from seaweed and CaOx crystals. However, this connection is well described for other molecules that also have negative charges in their structure, such as polyacrylate [32], osteopontin [38,39], glycosaminoglycans [40], and citrate [41]. Therefore, it can be confirmed, based on the data presented here and compared with those in the literature, that SPs seaweeds are able to alter the surface charge of CaOx crystals and thereby modify their crystallization dynamics.…”

Reconsidering Calcium Dehydration as the Rate-Determining Step in Calcium Mineral Growth

“…The dynamics of water molecules can be investigated using molecular dynamics (MD) simulations, for example, of water molecules around dissolved ions, ,− at mineral–water interfaces, − and in amorphous materials . Several studies have employed MD to study ion complexation and dynamics in water, − whereas the technique has also been used to analyze adsorption of small organics on mineral–water interfaces, , the structural changes in (water near) mineral interfaces, , and the influence of ion impurities on the kinetic stability of amorphous materials …”

Inhibition of Spiral Growth and Dissolution at the Brushite (010) Interface by Chondroitin 4-Sulfate

“…Prevention of kidney stones often involves the use of natural or synthetic macromolecules, including proteins, , peptides, , and polysaccharides, , through binding to the Ca-P or CaOx surfaces to inhibit crystal growth. As long unbranched polysaccharides, urinary glycosaminoglycans (GAGs) have been found to play an essential role in influencing stone formation. − Normal urine contains about 2% GAGs, which contain about 60% chondroitin sulfate (ChS). , Robertson and Scurr and Michelacci et al demonstrated that ChS promoted crystal nucleation in artificial urine, and Ryan et al reported that ChS had no effect on the deposition and aggregation of stone crystals, whereas in other published research works, − ChS was suggested to be a major inhibitor of crystal growth.…”

“…Figure5Bshows that the above equation fits to the step velocities along the [101] Cc direction. We, therefore, conclude that the interaction of the Ch4S-[101] Cc step is reasonably described by the C−V model, and this phenomenon was absent for both the [1̅ 00] Cc and [101̅ ] Cc steps (FigureS1), suggesting the presence of step-specific interactions by the negative carboxyl (−COO − ) and sulfonyl hydroxide (−SO 3 − ) groups of Ch4S binding to the calcium-terminated [101] Cc polar steps (FigureS3)41 through the geometry and stereochemistry of Ch4S matched to this polar step 25. 3.4.Step Density Changes.…”