The Flexible Polyelectrolyte Hypothesis of Protein−Biomineral Interaction

Abstract

Biomineralization is characterized by a high degree of control over the location, nature, size, shape, and orientation of the crystals formed. For many years, it has been widely believed that the exquisitely precise nature of crystal formation in biological tissues is the result of stereochemically specific interactions between growing crystals and extracellular matrix proteins. That is, the ability of many mineralized tissue proteins to adsorb to particular faces of biominerals has been attributed to a steric and electrical complementarity between periodic regions of the polypeptide chain and arrays of ions on the crystal face. In recent years, however, evidence has accumulated that many mineral-associated proteins lack periodic structure even when adsorbed to crystals. It also appears that protein-crystal interactions involve a general electrostatic attraction rather than arrays of complementary charges. In the present work, we review these studies and present some relevant new findings involving the mineral-modulating phosphoprotein osteopontin. Using molecular dynamics simulations, we show that the adsorption of osteopontin peptides to hydroxyapatite crystals does not involve a unique conformation of the peptide molecule, and that the adsorbed peptides are not aligned with rows of Ca(2+) ions on the crystal face. Further, we show that the interface between osteopontin peptides and calcium oxalate monohydrate crystals consists of peptide regions of high electronegativity and crystal faces of high electropositivity. Collectively, the above-mentioned studies suggest that interactions between mineral-modulating proteins and biologically relevant crystals are primarily electrostatic in nature, and that molecular disorder assists these proteins in forming multiple bonds with cations of the crystal face.

Citrate Modulates Calcium Oxalate Crystal Growth by Face-Specific Interactions

“…We recently proposed that inhibition of biomineral growth by proteins is governed by electrostatic interactions rather than stereochemical considerations [Hunter et al, 2010]. The results of the present study suggest that this may also be true for nonpolypeptide inhibitors.…”

Self-assembled peptide nanofibers on graphene oxide as a novel nanohybrid for biomimetic mineralization of hydroxyapatite

“…4a), it can be clearly seen that the obtained minerals show a macroporous structure with interconnected channels. According to previous studies, carboxylic acid and other groups on protein can serve as effective sites for nucleation and growth of HA crystals [26,42,43]. In this work, we suggest that the self-assembled PNFs bound onto GO nanosheets can provide enough nucleation sites for HA crystals, and help to concentrate the inorganic Ca 2+ in SBF, followed by the growth of HA.…”

The osteopontin-controlled switching of calcium oxalate monohydrate morphologies in artificial urine provides insights into the formation of papillary kidney stones

“…OPN is a polypeptide with a flexible backbone [12] and contains approximately 300 amino acids, many of which are aspartic or glutamic acid (including a sequence of contiguous aspartic acid residues) [13]. Human urinary OPN undergoes extensive posttranslational modification (glycosylation, phosphorylation, sulfation), exhibiting 31 phosphorylation sites and 5 Oglycans with approximately 8 of the 31 potential sites phosphorylated [14].…”