title: Altering biomineralization by protein design.
abstract: To create a bioceramic with unique materials properties, biomineralization exploits cells to create a tissue-specific protein matrix to control the crystal habit, timing, and position of the mineral phase. The biomineralized covering of vertebrate teeth is enamel, a distinctive tissue of ectodermal origin that is collagen-free. In forming enamel, amelogenin is the abundant protein that undergoes self-assembly to contribute to a matrix that guides its own replacement by mineral. Conserved domains in amelogenin suggest their importance to biomineralization. We used gene targeting in mice to replace native amelogenin with one of two engineered amelogenins. Replacement changed enamel organization by altering protein-to-crystallite interactions and crystallite stacking while diminishing the ability of the ameloblast to interact with the matrix. These data demonstrate that ameloblasts must continuously interact with the developing matrix to provide amelogenin-specific protein to protein, protein to mineral, and protein to membrane interactions critical to biomineralization and enamel architecture while suggesting that mutations within conserved amelogenin domains could account for enamel variations preserved in the fossil record.
authors.affiliation: University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
authors.forename: DanHong
authors.initials: D
authors.lastname: Zhu
authors.affiliation: University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
authors.forename: Michael L
authors.initials: ML
authors.lastname: Paine
authors.affiliation: University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
authors.forename: Wen
authors.initials: W
authors.lastname: Luo
authors.affiliation: University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
authors.forename: Pablo
authors.initials: P
authors.lastname: Bringas
authors.affiliation: University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033. Electronic address: mlsnead@usc.edu.
authors.forename: Malcolm L
authors.initials: ML
authors.lastname: Snead
mesh_terms: D000565:Ameloblasts / Q000737:chemistry; D053523:Amelogenin; D000818:Animals; D002516:Ceramics / Q000737:chemistry; D003743:Dental Enamel / Q000196:embryology* / Q000648:ultrastructure; D003746:Dental Enamel Proteins / Q000737:chemistry* / Q000235:genetics* / Q000502:physiology; D004285:Dogs; D018390:Gene Targeting; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D015202:Protein Engineering / Q000379:methods*; D013234:Stem Cells / Q000166:cytology
chemical_list: D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins