Abstract
Dental enamel is a unique composite bioceramic material that is the hardest tissue in the vertebrate body, containing long-, thin-crystallites of substituted hydroxyapatite. Enamel functions under immense loads in a bacterial-laden environment, and generally without catastrophic failure over a lifetime for the organism. Unlike all other biogenerated hard tissues of mesodermal origin, such as bone and dentin, enamel is produced by ectoderm-derived cells called ameloblasts. Recent investigations on the formation of enamel using cell and molecular approaches have been coupled to biomechanical investigations at the nanoscale and mesoscale levels. For amelogenin, the principle protein of forming enamel, two domains have been identified that are required for the proper assembly of multimeric units of amelogenin to form nanospheres. One domain is at the amino-terminus and the other domain in the carboxyl-terminal region. Amelogenin nanospheres are believed to influence the hydroxyapatite crystal habit. Both the yeast two-hybrid assay and surface plasmon resonance have been used to examine the assembly properties of engineered amelogenin proteins. Amelogenin protein was engineered using recombinant DNA techniques to contain deletions to either of the two self-assembly domains. Amelogenin protein was also engineered to contain single amino-acid mutations/substitutions in the amino-terminal self-assembly domain; and these amino-acid changes are based upon point mutations observed in humans affected with a hereditary disturbance of enamel formation. All of these alterations reveal significant defects in amelogenin self-assembly into nanospheres in vitro. Transgenic animals containing these same amelogenin deletions illustrate the importance of a physiologically correct bio-fabrication of the enamel protein extracellular matrix to allow for the organization of the enamel prismatic structure.
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Acknowledgments
We are grateful to all of our colleagues over past years, but in particular we would like to thank Dr. Janet Moradian-Oldak for her involvement in these studies. This work is supported by grants DE13045 and DE13404 from the NIH, the National Institute of Dental and Craniofacial Research.
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Paine, M.L., Lei, Y., Luo, W. et al. Perturbed Amelogenin Protein Self-assembly Alters Nanosphere Properties Resulting in Defective Enamel Formation. MRS Online Proceedings Library 823, W6.2 (2004). https://doi.org/10.1557/PROC-823-W6.2
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DOI: https://doi.org/10.1557/PROC-823-W6.2