Tooth enamel, made from tightly packed hydroxyapatite nanorods, is one of the hardest and most durable biomaterials known. Exactly how it is manufactured in the body is still a mystery. Now, a group led by George H. Nancollas at the State University of New York, Buffalo, has identified specific stages of enamel crystallization and found that the matrix protein amelogenin promotes hydroxyapatite nucleation (J. Phys. Chem. C, DOI: 10.1021/jp077105+). Much past research into enamel crystallization involved extreme conditions that do not reflect those in physiological systems. Nancollas and colleagues took a different tack by reducing experimental hydroxyapatite concentrations to slow down crystallization and investigating hydroxyapatite nucleation at physiological pH and temperature. The researchers found that the first step in their in vitro enamel production was the cooperative formation of composite nanospheres of nanocrystallite apatite and amelogenin. The composite nanoparticles then aggregated into nanorods that are about 50 nm in diameter and 250 nm long. The nanorods, in turn, further assembled to form organized, elongated crystals (shown). The findings indicate that amelogenin may play a critical role in controlling structural growth of enamel crystals, the researchers say.