CAREER: Molecular Level Investigation of Peptide Recognition on Hydroxyapatite

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This Career award by the Biomaterials program in the Division of Materials Research to University of California Berkeley is to develop a comprehensive understanding of the interactions between well-defined hydroxyapatite (HAP) crystals and their recognition peptides and how this mineralization is regulated. A molecular level understanding of how proteins regulate the biomineralization process is critical for understanding ossification, osteoporosis, and many other bone- and tooth-related diseases. With this project, the investigators will synthesize (100) and (001) HAP surfaces and study the surface structures of HAP crystals. The next step will be identification of peptides that specifically bind to the well-defined (100) and (001) surfaces and characterize their binding specificity under biologically relevant conditions. Using various microscopy and quantitative analysis techniques, the investigator will characterize the nanoscopic interactions between the recognition peptides and HAP crystal surfaces and verify the roles of the HAP-binding peptides. The successful completion of this research will provide specific recognition peptide motifs for well defined (100) and (001) HAP surfaces. The resulting HAP recognition peptides may be useful for designing hard tissue regenerating materials and/or for developing novel small molecule-based drugs to inhibit undesired mineralization processes. In addition, the proposed studies may be useful for developing protein-based bone prosthetic regeneration materials and novel therapeutics for bone related diseases such as osteoporosis and osteogenesis imperfecta.The educational aims of the project will provide learning opportunities for current and future researchers in bionanoscience and bioengineering. The PI will develop new courses at the undergraduate/graduate levels in the Department of Bioengineering, create a new seminar series on "Bionanoscience" at UC Berkeley, and organize conferences in local communities. A web-based database presenting the HAP-binding peptide sequences identified from phage display and in situ AFM analysis of the peptide interactions with HAP will be created. It will also provide researchers with an organized summary of other bone- and tooth- associated proteins. To encourage future generations to be engaged in science and engineering, the PI will work with undergraduate and graduate students to develop a hands-on exhibit and experiments to enhance the understanding of the role of proteins in bionanoscience using seashells and bones. This exhibit, entitled "Finding Nano", will be presented at the Lawrence Hall of Science Museum (Berkeley, CA), as well as to local low-income elementary schools.