Paper No. 1-4
Presentation Time: 9:00 AM
MODULATORS OF APATITE IN BONE FORMATION- ARE THEY PASSIVE OR ACTIVE?
Our lab uses in vitro model systems to examine the physicochemical mechanisms involved in biomineralization, with emphasis on the role biopolymers play in modulating mineral formation. In the biological realm, proteins are well known to have a high degree of specificity in their reactions because they have well-defined structures that provide molecular recognition in their ‘lock-n-key’ binding events. Therefore, it has long been assumed that highly specific interactions also occur between proteins and biomineralizing crystals, such as through epitaxial, charge matching or stereospecific interactions with specific crystal faces. Our studies, which started with the calcium carbonate system, have demonstrated that peptides that mimic the acidic proteins associated with biominerals (e.g. polyaspartate) can provide a high degree of control over mineral morphology through non-specific interactions, where the inhibitory activity of the polypeptides leads to a non-classical crystallization pathway which we called the polymer-induced liquid-precursor (PILP) process. The anionic polymer sequesters ion clusters, leading to liquid-liquid phase separation of nanodroplets in the crystallizing solution. The nanodroplets are so highly hydrated that they can flow and coalesce, enabling them to be molded into a variety of non-equilibrium crystal morphologies, many of which emulate the enigmatic features found in biominerals. In the calcium phosphate system, although proof of a liquid-phase precursor is less definitive, the evidence seems to support a PILP-like mechanism being involved in the mineralization of collagen during bone formation. This talk will illustrate, through our work and that of others, how the organization and alignment of the hydroxyapatite crystals in collagen may be achieved using processes that are far simpler than had long been assumed, perhaps involving only passive and non-specific interactions with both the collagen and non-collagenous proteins.