Without evidence for an organic framework, biological and biochemical processes observed during amelogenesis provided limited information on how extracellular matrix proteins control the development of the complex fibrous architecture of human enamel. Over a decade ago, amelogenin nanoribbons were first observed from recombinant proteins during in vitro mineralization experiments in our laboratory. In enamel from mice lacking the enzyme kallikrein 4 (KLK4), we later uncovered ribbon-like protein structures that matched the morphology, width, and thickness of the nanoribbons assembled by recombinant proteins. Interestingly, similar structures had already been described since the 1960s, when enamel sections from various mammals were demineralized and stained for transmission electron microscopy analysis. However, at that time, researchers were not aware of the ability of amelogenin to form nanoribbons and instead associated the filamentous nanostructures with possible imprints of mineral ribbons in the gel-like matrix of developing enamel. Further evidence for the significance of amelogenin nanoribbons for enamel development was stipulated when recent mineralization experiments succeeded in templating and orienting the growth of apatite ribbons along the protein nanoribbon framework. This article provides a brief historical review of the discovery of amelogenin nanoribbons in our laboratory in the context of reports by others on similar structures in the developing enamel matrix.
Keywords: apatite; biomineralization; developing enamel matrix; enamel; extracellular matrix; protein nanoribbons.