598 Salk Hall
3501 Terrace Street
Pittsburgh, PA 15261
- St. Petersburg State University, St. Petersburgh, Russia, MSc, Zoology, Biology (1992)
- Weizmann Institute of Science, Rehovot, Israel, PhD (1998)
Formation of interfaces between mineralized tissues (dentino-enamel interface)
Dentin and enamel are two mineralized tissues with strikingly different mechanical and structural properties that normally perform jointly for decades, without failure. Such an outstanding mechanical endurance requires an extraordinarily strong bond between these two tissues. Studies of tooth related genetic disorders and knockout animals demonstrate that the correct formation of the dentin-enamel interface is essential for proper tooth function. The problem of interface stability is also very important with respect to tissue repair, where implant failure often occurs due to a weak interface between tissues and repair materials. It is likely that interactions between dentin and enamel tissues during initial mineralization events play an important role in theproper formation of this critically important interface. My laboratory is interested in understanding basic processes involved in the formation of the dentin-enamel interface and how structural organization of this interface at nano-scale determines its unique mechanical properties. It is expected that the results of these studies will lead to the development of new advanced materials and procedures for mineralized tissue repair.
Role of biological macromolecules in the formation of mineralized tissues
Formation of biominerals in vertebrates occurs extracellularly and is regulated by complex assemblies of biological macromolecules. Besides their role in the regulation of biological mineralization these assemblies also serve as an integral component in many mineralized tissues (i.e., bones and dentin) contributing to their unique mechanical properties. Hence, the studies of mechanisms of supra-molecular assemblies in ECM are essential for our understanding of biomineralization processes as well as the functional properties of mature mineralized tissues.
One current area of research is the role of supramolecular protein assemblies in forming. Enamel is the hardest mineralized tissue in a human body, containing more than 95% of mineral. The organic matrix is transient and is removed upon enamel maturation. The enamel matrix, therefore, is thought to play a very minor, if any, functional role in mature enamel. The primary role of this matrix is believed to be the regulation of growth and organization of enamel crystals into intricate hierarchical structures. We are trying to understand how the enamel proteins organize into higher order structures that regulate arrangement of enamel crystals. In particular, we are interested in the interactions of enamel matrix molecules with minerals and the role of these interactions in the supramolecular assembly of the enamel matrix and the regulation of crystal growth.
Another focus area of our research is the role of acidic macromolecules in collagen mineralization. In collaboration with We are conducting a series of studies using recombinant acidic noncollagenous proteins of bone and dentin as well as their synthetic mimics. These studiesRole of the transient amorphous minerals in biomineralization processes
Transient amorphous minerals play an important role in biomineralization in many organisms. The transient amorphous calcium carbonate mineral phase is present in developing skeletons of echinoderms and mollusks. Amorphous calcium phosphate is found in matrix vesicles that are associated with initial stages of formation of cartilage, bone, dentin and probably enamel. It is still not clear exactly what role amorphous calcium phosphate plays in mineralization. However, there is growing consensus that it is essential for initiation of the mineralization process. From the point of view of mineralization strategies, stabilized amorphous phases provide unique opportunities for transporting of large quantities of mineral ions to the mineralization site—avoiding the danger of spontaneous mineral precipitation in undesirable locations. These amorphous phases can be transformed into crystalline mineral in a controlled manner either by overgrowth of pre-existing seed crystals or by regulated breakdown of stabilizing agents. We are currently exploring the role of such transient mineral phases in enamel formation. We are hopeful that such insight will prove to be useful in the development of applications that use transient amorphous calcium phosphate phases for hard tissue restoration and provide new technologies for treatment and repair of tooth decay.
Kwak, S.-Y., F.B. Wiedemann-Bidlack, E. Beniash, Y. Yamakoshi, J.P. Simmer, A. Litman, and H.C. Margolis, 2009. Role of 20-kDa Amelogenin (P148) Phosphorylation in Calcium Phosphate Formation in Vitro. J. Biol. Chem. 284: 18972-18979.
Beniash, E., R.A. Metzler, R.S.K. Lam, and P.U.P.A. Gilbert, 2009. Transient amorphous calcium phosphate in forming enamel. J. Struct. Biol. 166: 133-143.
Deshpande, A.S., and E. Beniash, 2008. Bioinspired Synthesis of Mineralized Collagen Fibrils. Cryst. Growth Des. 8: 3084-3090.
Baldassarri, M., H.C. Margolis, and E. Beniash, 2008. Compositional determinants of mechanical properties of enamel. J. Dent. Res. 87: 645-649.
Elangovan, S., H.C. Margolis,
F.G. Oppenheim, and E. Beniash, 2007. Conformational
Changes in Salivary Proline-Rich Protein 1 upon
Adsorption to Calcium Phosphate
Wiedemann-Bidlack, F.B., E. Beniash, Y. Yamakoshi, J.P. Simmer, and H.C. Margolis, 2007. pH triggered self-assembly of native and recombinant amelogenins under physiological pH and temperature in vitro. J. Struct. Biol. 160: 57-69.
Margolis HC, Beniash E, Fowler CE. 2006. Role of macromolecular assembly of enamel matrix proteins in enamel formation. J. Dent. Res. 85(9):775–793.
Beniash E, Skobe Z, Bartlett JD. 2006. Formation of the dentino-enamel interface in enamelysin (MMP-20) deficient mouse incisors. Eur. J. Oral Sci. 114(Suppl. 1) :24–29.
Beniash E, Hartgerink JD, Storrie H, Stendahl JC, Stupp SI. 2005. Self-assembling peptide amphiphile nanofiber matrices for cell entrapment. Acta Biomaterialia 1 (4):387–397.
Beniash E, Simmer JP, Margolis HC. 2005. Effects of recombinant mouse amelogenins on the formation and organization of hydroxyapatite crystals in vitro. J. Struct. Biol. 149(2):182–190.
Hartgerink JD, Beniash E, Stupp SI. 2002. Peptide-amphiphile nanofibers: A flexible scaffold for the preparation of materials. Proc. Natl. Acad. Sci. 99 (8):51 33–51 38.
Hartgerink JD, Beniash E, Stupp SI. 2001. Self-assembly and mineralization of peptide-amphiphile nanofibers. Science 294(5547):1 684–1688.
Beniash E, Traub W, Veis A, Weiner S. 2000. A transmission electron microscope study using vitrified ice sections of predentin: Structural changes in the dentin collagenous matrix prior to mineralization. J. Struct. Biol. 132(3):212–225.
Beniash E, Aizenberg J, Addadi L, Weiner S. 1997. Amorphous calcium carbonate transforms into calcite during sea urchin larval spicule growth. Proc. R. Soc. London, Ser. B 264:461 –465.