Tooth Amelogenesis How Nature Manufactures the Hardest Material in the Human Body:
Tooth enamel is an extraordinary biomaterial equally attractive to dentists and to bioengineers.Yet, to this date, the mechanisms responsible for the formation of this unusual bioceramic have remained enigmatic. It is well established that the first crystals that eventually turn into the enamel mineral phase develop within an aqueous protein matrix. In recent studies, we have mapped the changes in protein composition and localization within this matrix during enamel development using proteomics and immunohistochemistry, and examined the effect of the major tooth enamel protein, amelogenin, on enamel crystal growth using conventional electron microscopy. To overcome the artifacts introduced when using conventional electron microscopy, we have placed early enamel matrix preparations into a liquid chamber environment that allowed us to obtain unprecedented insights into enamel protein/mineral relationships during the earliest stages of amelogenesis. To identify the role of individual protein domains on enamel crystal growth, we have determined the complete structure of the principal enamel protein, amelogenin, using 3D NMR. Our structure/function studies have associated the amelogenin N-terminus with matrix self assembly, the C-terminus with protein adhesion to the crystal surface, and the polyproline-rich region with crystal elongation. We will conclude our presentation with a brief overview of current engineering strategies suitable for the manufacture of this most fascinating biomaterial, including cellular and synthetic approaches.