Computational Modeling Speeds Researchers’ Discovery in the Building Blocks of Human Enamel

In contrast to his renowned athleticism, battlefield fortitude and expeditionary zeal, George Washington suffered failing teeth throughout his adult life. Letters and diary entries catalog miseries including aching teeth, lost teeth, inflamed gums and ill-fitting dentures. While the tale of Washington’s wooden teeth is a myth, the physical and social constraints imposed by his ailing teeth and dentures were very real.

Thanks to advances in modern dentistry, tooth decay is less likely to become debilitating. Nonetheless, tooth decay remains a costly public health concern, growing in importance as the population ages. According to the U.S. Centers for Disease Control and Prevention, about one-fourth of children, half of adolescents and more than 90% of adults have experienced tooth decay. One in five adults ages 65 or older has untreated tooth decay, as reported in a January 2020 Harvard Health Letter. When left untreated, tooth decay can lead to a severe infection under the gums that can spread to other parts of the body, such as the brain or heart, with serious and in rare cases fatal results.

It turns out that the best way to understand how human enamel decays is to understand how it’s formed. Prasanna Balachandran, assistant professor of materials science and engineering with a joint appointment in mechanical and aerospace engineering at the University of Virginia, is doing just that as a member of a research team led by Northwestern University’s Derk Joester, associate professor of materials science and engineering. Balachandran’s results fed into the research team’s finite element modeling of human enamel. The knowledge they generate should aid the development of new interventions and materials to prevent and treat tooth decay and may also help prevent or lessen the suffering of patients with congenital enamel defects.

While our appetites may increase our risk of tooth decay, our apatites—nanoscale crystallites that are the fundamental building blocks of enamel—are key to healthy teeth. Balachandran has worked with apatites, one of the subjects of his dissertation research, for several years. His group at UVA has been investigating the fundamental question of how different elemental substitutions affect the thermodynamic stability and formability of apatite compounds. Their research aims to improve materials’ performance in extreme environments; identify solid-state electrolytes for fuel cell technologies; and immobilize toxic elements so that they cannot leech into soil or water.

Connecting with Joester and his team has opened the door to pursue an exciting new research direction in the domain of dental materials. Perhaps unique to human enamel, the center of the hydroxylapatite crystallite seems to be more soluble, Joester said, and his team wanted to understand why. The researchers set out to test if the composition of minor enamel constituents varies in single crystallites.

Like the enamel itself, atomistic interactions of human enamel’s building blocks are dauntingly complex. This is where Balachandran’s computational modeling, in collaboration with James Rondinelli’s group at Northwestern University, came into play. Their density functional theory calculations encompassing 350 atoms helped researchers selectively isolate and understand which interactions are significant, such as what happens when magnesium ions replace calcium ions in hydroxylapatites.

Joester’s group was the first to quantitatively map the minor ions such as magnesium, carbonate, fluoride and sodium across single crystallites. Balachandran’s calculations allowed Joester’s team to better understand what the presence of the ions means for crystallites, and more specifically, how the concentration of these ions affects properties important to the strength of human enamel.

Using cutting-edge quantitative atomic-scale techniques, Joester’s team discovered that human enamel crystallites have a core-shell structure. Each crystallite has a continuous crystal structure with calcium, phosphate and hydroxyl ions arranged periodically (the shell). However, at the crystallite’s center, a greater number of these ions is replaced with magnesium, sodium, carbonate and fluoride (the core). Within the core, two magnesium-rich layers flank a mix of sodium, fluoride and carbonate ions.

“Even though calcium and magnesium are related elements, magnesium ions are much smaller than calcium ions,” Balachandran said. “When magnesium ions substitute for calcium ions, their natural reaction is to compress or constrict.” The presence of magnesium leads to contraction of the crystal at its core. The shell is crammed into a smaller space than it likes while the core is stretched further apart than it likes.

“Without Prasanna’s calculations, we would not have known how much the crystallite contracts given the amount of magnesium we observed, and so the finite element calculations would not have been possible, or at least we would not have known the absolute magnitude of the stresses,” Joester said. Compressive stresses act to close cracks and hinder their propagation, which in turn increases the strength of a material and prevents fatigue. Balachandran’s calculations supported the researchers’ proposal that the core-shell structure of enamel may be linked to its remarkable resilience.  

High local stresses make a material more soluble. From their finite element model, Joester’s team noted that an area of high stress is present at the end of the crystal. This observation likely explains why the crystal core dissolves faster. “We now know that the chemical composition of the core, via the effect of individual ions on the crystal structure that Prasanna calculated, impacts enamel properties that are important for tooth decay,” Joester explained.

The team presents their findings in “Chemical Gradients in Human Enamel Crystallites,” published in the journal Nature on July 1, 2020. Grants from the National Institute of Dental and Craniofacial Research at the National Institutes of Health and the National Science Foundation supported this research.