Something to chew on: hard facts about tooth enamel

Science News, May 14, 2005 by Alexandra Goho

If you're not sitting in the dentist's office reading this article, chances are that your tooth enamel is doing its job, at least for now. This protective ceramic-like veneer, thick as a dime, is the strongest material in the human body. It's your teeth's first line of defense against corrosive bacteria and the constant pounding and stresses that come with chewing.

Strong as it is, enamel is also brittle. What keeps it from shattering is an underlying protein-rich layer of dentin, a softer, more compliant substance that acts like a shock absorber. "If you had enamel sitting on a hard surface, every time you'd bite down on it, it would crack," says Arthur Veis, a molecular biologist at Northwestern University in Evanston, Ill.

Enamel is one of the trickiest dental tissues to mimic, but it's a necessary component for creating synthetic stand-ins or repair kits for teeth. Over the years, a variety of ceramics and metals have been used as fillings, crowns, and other dental implants, but they lack the strength of enamel and often crack, dislodge, or wear down. Dental materials gone bad are a common clinical problem. According to the American Dental Association based in Chicago, dentists spend more than 50 percent of their time restoring damaged or decaying teeth and about two-thirds of these procedures are for replacing dental materials that have failed.

Investigators have made several attempts to grow enamel from the cell that make it within the gums, but "nobody has really demonstrated true enamel," says Pamela Robey of the National Institute of Dental and Craniofacial Research in Bethesda, Md.

Researchers have isolated several of the other cell types involved in tooth development. They have used these cells to regenerate dentin; cementum, which is the hard tissue on root surfaces; and the periodontal ligament that attaches each tooth to the jaw. "The one thing that's missing now is enamel," says Robey.

With several recent discoveries, researchers have gotten the best glimpse yet of enamel in formation. Thanks to advances in materials science as well, they're closer than ever to making synthetic enamel that can compete with nature's version. With that, they hope to reach an even more audacious goal: growing an entire tooth from scratch.

SWIFT ASSEMBLY The primary ingredient of both enamel and dentin is the calcium phosphate mineral called hydroxyapatite. Yet these two dental tissues have dramatically different properties. That's because about 40 percent of dentin consists of protein, whereas enamel is almost devoid of organic material. Like a dinner plate, tooth enamel is almost pure ceramic.

That property has long puzzled researchers. Nearly all biomineralized structures found in nature, from mollusk shells to bone, rely on proteins for their assembly. The proteins serve as scaffolds that guide crystal growth, often resulting in elaborate shapes and structures (SN: 7/17/04, p. 42). In the case of dentin, long and narrow crystals of hydroxyapatite grow along rod-shaped molecules of collagen, a particularly abundant structural protein in the body. The collagen becomes an integral part of dentin and counters hydroxyapatite's inherent brittleness.

For years, researchers have had good reason to suspect that a protein called amelogenin contributes to the growth of enamel in gums. Studies showed that defective amelogenin proteins lead to the disease amelogenesis imperfecta. In that disorder, tooth enamel doesn't form properly, leaving teeth discolored and vulnerable to damage. What's more, says Janet Moradian-Oldak of the School of Dentistry at the University of Southern California in Los Angeles, "a single mutation in the sequence of the gene that codes for amelogenin can completely destroy enamel structure."

At first glance, amelogenin looks all wrong for the job of crystal growth. It's about one-tenth the size of collagen and doesn't have the rodlike shape of the hydroxyapatite crystals in enamel. Researchers such as Moradian-Oldak have tried to study amelogenin in animals, but the protein disappears almost as soon as the cells make it.

About a decade ago, she and her colleagues came upon a clue to how amelogenin might work in the formation of enamel. While observing the protein under a microscope, the researchers watched it form spontaneously into tiny spheres about 20 nanometers in diameter. Each sphere consisted of a cluster of some two dozen individual protein molecules. Intriguing as the finding was, it seemed unlikely that these spheres could have much to do with enamel's long, narrow crystals.

Reporting in the March 4 Science, Moradian-Oldak and Guiseppe Falini at the University of Bologna in Italy appear to have finally uncovered amelogenin's mineral-forming properties.

First, when the researchers added the protein to a solution that closely matched the physiological conditions in gums, the proteins spontaneously assembled into nanospheres like those Moradian-Oldak had seen years ago. That's not all that happened.

The nanospheres joined to form chains. Then, the chains aligned themselves to form microribbons several hundred microns in length and about 30 microns wide. Using both a transmission electron microscope and an atomic-force microscope, the researchers mapped out the fine details of this protein-assembly process.