Altering biomineralization by protein design.
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.
Zhu
DanHong
D
University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
Paine
Michael L
ML
University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
Luo
Wen
W
University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
Bringas
Pablo
P
University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033.
Snead
Malcolm L
ML
University of Southern California, Center for Craniofacial Molecular Biology, Los Angeles, California 90033. Electronic address: mlsnead@usc.edu.
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
D053523:Amelogenin; C507200:Amelx protein, mouse; D003746:Dental Enamel Proteins