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April 2009

Something To Smile About

Pacific Northwest National Laboratory researchers elucidate first steps in tooth formation

Child with lost tooth
A research team from Pacific Northwest National Laboratory and the University of Southern California’s Center for Craniofacial Molecular Biology discovered one of the initial steps the body takes to build tooth enamel.

Results:  Thousands of people who suffer from inherited tooth defects are one step closer to showing off their smiles, thanks to a research team from Pacific Northwest National Laboratory and the University of Southern California's Center for Craniofacial Molecular Biology.  The team discovered one of the initial steps the body takes to build tooth enamel, which could help in the prevention and treatment of defective enamel formation.

Why it Matters: The findings might help in the treatment of amelogenesis imperfecta, a tooth disorder that leaves both baby and permanent teeth with little or no enamel.  The condition, which afflicts more than 14,000 people in the United States alone, causes teeth to be small, discolored, hypersensitive to temperature changes, and subject to extensive damage.  Besides the obvious discomfort, amelogenesis imperfecta can have psychological effects.  Treatment of the disorder can be complicated, expensive, and painful. 

Methods: Using nuclear magnetic resonance instruments and other resources at EMSL, a national scientific user facility at PNNL, the team focused on amelogenin, a unique protein that plays a major role in the formation of tooth enamel.  They determined the initial steps in how amelogenin self assembles into tiny spheres called nanospheres. The spheres are about 20 nanometers, a billionth of a meter, in diameter and interact with the primary mineral compound found in enamel (hydroxyapatite) to form long, ribbon-like crystals 3000 times longer than those found in bone.  The elongated crystals, formed into a woven pattern, give enamel the strength to last a lifetime. 

The team studied the initial steps of amelogenin matrix formation in solutions with and without salt.  Without salt in the solution, amelogenin exists as monomers, or small individual molecules.  Two salts were tested, sodium chloride (table salt) and calcium chloride (used in creating cement and to combat icy roads), and both resulted in similar amelogenin interaction.  When salt was added, amelogenin monomers began to form pairs or dimers.  Dimer formation is the first step in amelogenin assembly.

"Our research provides a better comprehension of the formation of nanospheres," said Dr. Wendy Shaw, a member of the research team at PNNL.  "The knowledge we've gained establishes the mechanistic groundwork essential for developing enamel replacements."

What's Next:  Scientists continue to work on re-creating natural enamel in the laboratory, which could aid in the repair of tooth decay or damage.  This is an enormous challenge because amelogenin disappears by the time the tooth breaks through the gum and, unlike skin or bone, can no longer regenerate.  Some researchers are successfully growing the internal material of teeth (dentin) in laboratory animal experiments, but the ability to duplicate enamel's mineralization process in the lab does not exist. 

"We don't have the capability to produce enamel outside of the body, but we're learning what happens at the molecular level," Shaw said.  "This fundamental understanding is necessary to provide major advancements in enamel restoration in the next 10-20 years."   

Acknowledgments: The National Institute of Dental and Craniofacial Research, part of the National Institutes of Health, supported the research. 

The research team was Garry Buchko, Jacky Bekhazi, Barbara Tarasevich, and Wendy Shaw at PNNL, Richland; and Malcolm Snead of the Center for Craniofacial Molecular Biology, University of Southern California, Los Angeles. 

Reference: Buchko GW, BJ Tarasevich, JG Bekhazi, ML Snead, and WJ Shaw. 2008. "A Solution NMR Investigation into the Early Events of Amelogenin Nanosphere Self-Assembly Initiated with Sodium Chloride or Calcium Chloride." Biochemistry 47(50):13215-13222. doi: 10.1021/bi8018288.

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