The goal of this proposal is to advance our understanding of the fundamental molecular mechanisms involved in the formation of dental enamel, with an emphasize on the nanoscale structure and function of the proteins of the secretory stage enamel matrix and its contained arrays of amelogenin """"""""Nanospheres."""""""" We postulate that such understanding will lead to the future development of biomimetic strategies for the creation of enamel-like mineral materials. Our general hypothesis is: Amelogenin primary structure defines amelogenin quaternary structures (nanospheres) which in turn direct enamel matrix supramolecular architecture facilitating the postnucleation growth of carbonated hydroxyapatite enamel crystals. This biomineralization process is affected through two major molecular mechanisms: (1) amelogenin-protein interactions resulting in the organization of the enamel extracellular matrix and defining the spatial environment, and, (2) protein-mineral interactions, inhibiting premature crystal-crystal fusion and promoting the controlled and oriented growth of the enamel crystals. We propose to examine this hypothesis with the following Specific Aims: 1. Using recombinant and native enamel proteins (amelogenins, enamelins and ameloblastin), to identify the nature of the interactions which define protein self-assembly in solution and the nanosphere matrix architecture, at the molecular level. 2.Using recombinant and native enamel proteins to define, at the supramolecular level, the ultrastructural architecture of amelogenin-gel matrices formed in vitro in the presence and absence of enamelins and ameloblastin proteins. 3. To characterize apatite and octacalcium phosphate crystal growth, morphology and orientation within synthetic amelogenin gel matrices in the absence and presence of the non-amelogenins. 4. To characterize the effects of amelogenin and non-amelogenins on apatite and octacalcium crystal growth morphology in solution, determining the nature of molecular interactions of the proteins with these calcium phosphate crystals. 5. To define, at the supramolecular level, the ultra structural architecture of amelogenin-gel matrix in vivo and to determine the localization of enamel proteins and their relation to the mineral phase. In summary, considering tooth enamel as a tissue that may be restored with biomimetic strategies, it is envisaged that the knowledge and information gained from these proposed studies will provide the inspiration for material scientists to design and develop novel and improved biomaterials.
| Prajapati, S; Ruan, Q; Mukherjee, K et al. (2018) The Presence of MMP-20 Reinforces Biomimetic Enamel Regrowth. J Dent Res 97:84-90 |
| Mukherjee, Kaushik; Ruan, Qichao; Nutt, Steven et al. (2018) Peptide-Based Bioinspired Approach to Regrowing Multilayered Aprismatic Enamel. ACS Omega 3:2546-2557 |
| Klein, Ophir D; Duverger, Olivier; Shaw, Wendy et al. (2017) Meeting report: a hard look at the state of enamel research. Int J Oral Sci 9:e3 |
| Ruan, Qichao; Liberman, David; Zhang, Yuzheng et al. (2016) Assembly of Layered Monetite-Chitosan Nanocomposite and Its Transition to Organized Hydroxyapatite. ACS Biomater Sci Eng 2:1049-1058 |
| Ren, Dongni; Ruan, Qichao; Tao, Jinhui et al. (2016) Amelogenin Affects Brushite Crystal Morphology and Promotes Its Phase Transformation to Monetite. Cryst Growth Des 16:4981-4990 |
| Mazumder, P; Prajapati, S; Bapat, R et al. (2016) Amelogenin-Ameloblastin Spatial Interaction around Maturing Enamel Rods. J Dent Res 95:1042-8 |
| 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 |
| 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 75:260-270 |
| Bauskar, Aditi; Mack, Wendy J; Mauris, Jerome et al. (2015) Clusterin Seals the Ocular Surface Barrier in Mouse Dry Eye. PLoS One 10:e0138958 |
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