This proposal is based on the perceived need for the design and development of new biomaterials that will be utilized in repair and regeneration of tooth enamel. The major objective of our proposed study is to elucidate the molecular mechanisms involved in the formation of dental enamel with a particular emphasize on the supramolecular assembly, structure and function of the extra cellular components;amelogenin, enamelin and ameloblastin. The long-term goal is to develop biomimetic strategies for the fabrication of enamel-like materials in in vitro and in cell free systems. Our general hypothesis is that the highly organized carbonated hydroxyapatite crystals in enamel are formed through complex arrays of protein-protein and protein-mineral interactions primarily controlled by the supramolecular "chain assembly" of amelogenin nanospheres interacting with the structural motifs within enamelin and/or ameloblastin. The formation of amelogenin nanospheres and their further assembly into linear arrays are promoted by the unique secondary structure of amelogenin proteins.
Specific aims : I. To investigate the nanosphere chain assembly of amelogenin in vivo and in vitro, and to elucidate secondary structure preferences within the amelogenin sequence in vitro. II. To determine the secondary structures of the 32kDa enamelin and ameloblastin fragments and to investigate their interactions with the chains of amelogenin nanosphres in vivo and in vitro. III. To investigate the interaction of amelogenin "chain assemblies" with calcium phosphate minerals in vitro, in the presence of non-amelogenins, and to develop biomimetic models for fabrication of enamel-like nanocomposites. In Summary: The principal molecular mechanisms learned from our investigation proposed in aims l-lll will contribute to our understanding of the structural biology of enamel extracellular matrix in vivo, and will provide a solid ground for the design and development of improved materials with potential application in dental and medical field. Moreover, this study will have a significant impact on the field of biomineralization, molecular self-assembly, protein structure, and understanding of pathological enamel formation.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE013414-09
Application #
8006394
Study Section
Musculoskeletal Tissue Engineering Study Section (MTE)
Program Officer
Lumelsky, Nadya L
Project Start
1999-12-01
Project End
2013-06-13
Budget Start
2011-02-01
Budget End
2013-06-13
Support Year
9
Fiscal Year
2011
Total Cost
$375,409
Indirect Cost
Name
University of Southern California
Department
Dentistry
Type
Schools of Dentistry
DUNS #
072933393
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Ruan, Qichao; Liberman, David; Bapat, Rucha et al. (2016) Efficacy of amelogenin-chitosan hydrogel in biomimetic repair of human enamel in pH-cycling systems. J Biomed Eng Inform 2:119-128
Prajapati, Saumya; Tao, Jinhui; Ruan, Qichao et al. (2016) Matrix metalloproteinase-20 mediates dental enamel biomineralization by preventing protein occlusion inside apatite crystals. Biomaterials 75:260-70
Su, Jingtan; Chandrababu, Karthik Balakrishna; Moradian-Oldak, Janet (2016) Ameloblastin peptide encoded by exon 5 interacts with amelogenin N-terminus. Biochem Biophys Rep 7:26-32
Mazumder, P; Prajapati, S; Bapat, R et al. (2016) Amelogenin-Ameloblastin Spatial Interaction around Maturing Enamel Rods. J Dent Res 95:1042-8
Ruan, Qichao; Moradian-Oldak, Janet (2015) Amelogenin and Enamel Biomimetics. J Mater Chem B Mater Biol Med 3:3112-3129
Bauskar, Aditi; Mack, Wendy J; Mauris, Jerome et al. (2015) Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye. PLoS One 10:e0138958
Lokappa, Sowmya Bekshe; Chandrababu, Karthik Balakrishna; Dutta, Kaushik et al. (2015) Interactions of amelogenin with phospholipids. Biopolymers 103:96-108
Lokappa, Sowmya Bekshe; Chandrababu, Karthik Balakrishna; Moradian-Oldak, Janet (2015) Tooth enamel protein amelogenin binds to ameloblast cell membrane-mimicking vesicles via its N-terminus. Biochem Biophys Res Commun 464:956-61
Ruan, Qichao; Siddiqah, Nadia; Li, Xiaochen et al. (2014) Amelogenin-chitosan matrix for human enamel regrowth: effects of viscosity and supersaturation degree. Connect Tissue Res 55 Suppl 1:150-4
Chandrababu, Karthik Balakrishna; Dutta, Kaushik; Lokappa, Sowmya Bekshe et al. (2014) Structural adaptation of tooth enamel protein amelogenin in the presence of SDS micelles. Biopolymers 101:525-35

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