Elia Beniash, PhD





  693 Salk Hall
  3501 Terrace Street
  Pittsburgh, PA 15261

  Associate Professor

  Department of Oral Biology
  School of Dental Medicine


  St. Petersburg State University, St. Petersburg, Russia, MSc, 1992, Zoology, Biology

  The Weizmann Institute of Science, Rehovot, Israel, PhD, 1998, Structural Biology, Chemistry



Biogenic mineralized materials—such as those found in bones and teeth—are produced by organisms ranging from bacteria to higher plants and mammals. The main role of these “biominerals” is mechanical reinforcement of tissues and organs. They often have properties superior to those of synthetic materials, a fact that is especially fascinating given a limited spectrum of conditions in which biological systems can effectively operate. The secret to the efficiency of biominerals is their sophisticated structure. We seek to understand the basic mechanisms of control by which organisms form these materials. We believe that this understanding will help us design advanced organo-mineral composite materials to be used in repairing hard tissue, such as enamel, dentin, and bone. Novel ways of manufacturing tissue-repair materials using strategies found in nature have recently received much attention. Interest in this field has been accelerated by successes in nanotechnology that should help to revolutionize the field of restorative medicine. The general consensus among scientists is that this approach will provide biocompatible materials with structural and mechanical properties that match those of biological tissues. Our studies are focused on understanding basic strategies of mineralization in biological systems and on applying those strategies to the design of new, nano-structured, bio-inspired composite materials.


Current Areas of Research

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 the proper 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 (in collaboration with Dr. Margolis, Forsyth Institute, Cambridge, MA)

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 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 Dr. Sfeir (University of Pittsburgh, School of Dental Medicine), we are conducting a series of studies using recombinant acidic noncollagenous proteins of bone and dentin, as well as their synthetic mimics. These studies provide critical insight into the basic mechanisms of bone and dentin mineralization and provide inspiration for nanostructured materials for mineralized tissue repair and regeneration.


Role 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.


Effects of ocean acidification on the marine calcifiers (In collaboration with Dr. Sokolova, UNC, Charlotte, NC)

Increasing levels of atmospheric carbon dioxide (CO2) lead to an increase of its partial pressure in the surface layers of the ocean. Seawater is a carbonate buffer, and increases in the levels of dissolved CO2 can cause a significant drop in seawater pH and calcium carbonate saturation. This ocean acidification can affect marine calcifiers such as mollusks, corals and echinoderms that build their skeletons from calcium carbonate (CaCO3). Because biomineralization is a tightly regulated process, ocean acidification would likely affect the rates of CaCO3 deposition and dissolution, as well as structural, compositional and mechanical properties of their shells. Marine calcifiers produce two major polymorphs of calcium carbonate: calcite and aragonite. The more stable calcite is found in many phyla, including foraminifera, coccolithophores and echinoderms, while most corals build skeletons from aragonite. Mollusks use both polymorphs; some produce purely calcitic or aragonitic shells, while others combine the two. Aragonite is more soluble than calcite, suggesting that ocean acidification will have different impacts on marine calcifiers with different skeletal mineralogies.  We explore the effects of elevated CO2 on three major North American mollusk species with different shell mineralogies: eastern oysters (calcitic), hard shell clams (aragonitic), and blue mussels (mixed calcitic/aragonitic). These important mollusks serve as ecosystem engineers in estuarine and coastal habitats and are key species for fisheries and aquaculture in the eastern United States. Our multidisciplinary approach combines investigations of molluskan physiology with studies of shells’ deposition rates, structural organization, mineralogy and mechanical properties. It will provide information on how CO2 level affect shell calcification, and reveal physiological mechanisms by which elevated CO2 levels affect marine calcifiers.


Bioinspired adhesives based on the barnacle cement (in collaboration with Dr. Ellen Gawalt, Duquesne University, Pittsburgh, PA)

Developing adhesives that can cure rapidly in an aqueous environment is a difficult task, yet is of critical importance for surgical and dental application. These glues must provide outstanding adhesive strength, while at the same time being biologically benign. In addition, surgical and dental adhesives often need to secure two dissimilar materials, such as a metal implant to bone or tooth.

Barnacles produce a unique glue which strongly adheres to virtually any surface. This glue comprises self-assembled protein nanofibrils, which form via mechanism similar to that of blood clotting. Upon pulling the glue can dissipate large amounts of energy via hidden length/sacrificial bond mechanism, based on a supramolecular network held together by reversible non-covalent (hydrophobic) and possibly covalent (disulfide) bonds. Although some of the molecules comprising this glue were identified, the exact chemical mechanism of its adhesiveness remains unknown.

We study the chemical composition and the mechanisms of adhesion of the barnacle glue and apply this knowledge for bioinspired design of novel adhesive materials for biomedical applications.



Ping-An Fang, James F. Conway, Henry C. Margolis, James P. Simmer, Elia Beniash. Hierarchical Self-Assembly of Amelogenin and the Regulation of Biomineralization at the Nanoscale. PNAS [in press]

Deshpande, Atul; Fang, Pingan; Zhang, Xiaoyuan; Jayaraman, Thottala; Sfeir, Charles; Beniash, Elia. Primary Structure and Phosphorylation of Dentin Matrix Protein 1 (DMP1) and Dentin Phosphophoryn (DPP) Uniquely Determine Their Role in Biomineralization. Biomacromolecules [in press]

E. Le Norcy,  S-Y. Kwak, F. B. Wiedemann-Bidlack, E. Beniash, Y. Yamakoshi,  J. P. Simmer, H.C. Margolis Potential Role of the Amelogenin N-terminus in the Regulation of Calcium Phosphate Formation In Vitro.  Cells Tissues Organs  [Epub ahead of print]

Ping-An Fang,  Henry C. Margolis, James F. Conway,  James P. Simmer, Gary H. Dickinson,  Elia Beniash. Cryogenic Transmission Electron Microscopy Study of Amelogenin Self-Assembly at Different pH. Cells Tissues Organs  2011 May 20. [Epub ahead of print]

Tomanek L, Zuzow MJ, Ivanina AV, Beniash E, Sokolova IM. Proteomic response to elevated PCO2 level in eastern oysters, Crassostrea virginica: evidence for oxidative stress. J Exp Biol. 2011 Jun 1;214(Pt 11):1836-44.

Watkins, M., S. K. Grimston, Norris, J. Y., Guillotin, B., Shaw, A., Beniash, E., Civitelli, R. et al. Osteoblast connexin43 modulates skeletal architecture by regulating both arms of bone remodeling. 2011, Molecular Biology of the Cell 22(8): 1240-1251.

Elia Beniash, Atul Deshpande, Ping An Fang, Nicholas Lieb , Xiaoyuan Zang, Charles Sfeir Possible role of DMP1 in dentin mineralization. 2011 Journal of Structural Biology, 3 (1): 47-69

Beniash E. Biominerals- hierarchical nanocomposites: the example of bone. 2011 WIREs Nanomedicine & Nanobiotechnology, 3 (1): 47-69   

Felicitas B Wiedemann-Bidlack; Seo-Young Kwak; Elia Beniash; Yasuo Yamakoshi; James P Simmer, Henry C. Margolis Effects of phosphorylation on the self-assembly of native full-length porcine amelogenin and its regulation of calcium phosphate formation in vitro. 2011  Journal of Structural Biology 173 (2):250-260

Elia Beniash, Anna Ivanina, Nicholas S. Lieb1, Ilya Kurochkin, Inna M. Sokolova Elevated level of carbon dioxide affect metabolism and shell formation in oysters Crassostrea virginica (Gmelin). 2010 MEPS 419: 95–108

Deshpande A.S., Fang P.A., Simmer J.P., Margolis H.C., Beniash E. Amelogenin-collagen interactions regulate calcium phosphate mineralization in vitro. (2010) J Biol Chem.; 285(25):19277-87 PMID: 20404336

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 Crystals. Langmuir 23: 11200-11205.

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.

Bartlett JD, Beniash E, Lee DH, Smith CE. 2004. Decreased mineral content in MMP-20 null mouse enamel is prominent during the maturation stage. J. Dent. Res. 83(1 2):909–913.

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.