Organisms have had eons to refine their materials.

Once enamel is deposited on the surface of our teeth, the cells that built it die. After eruption it can survive a century or more of the conditions inside the mouth: hundreds of millions of chewing cycles, acidic and abrasive foods, repeated swings in temperature. It is considered the most durable of biological materials, and in fossils it preserves usable information for more than 40 million years.

Things can go awry during development, as in the rare inherited disorder amelogenesis imperfecta, or the far more common molar hypomineralization — "chalky teeth". They can also go wrong after eruption, when enamel is the first tissue damaged by erosive wear and by tooth decay. These conditions are rarely life-threatening, but their burden on patients and on society is enormous. Dental expenditure in the United States is approaching $200 billion a year, and around three billion people worldwide have untreated caries.

What makes enamel both fascinating and hard to understand is that its properties arise from a hierarchical architecture spanning many length scales. It is built from highly elongated crystallites only tens of nanometers across, each like a strand of uncooked spaghetti. Tens of thousands of these are bundled into rods, and the rods are woven together to form the enamel layer. As we and others have learned over the past decade, the hierarchy continues below the crystallite itself. Crystallites are joined by a vanishingly thin amorphous inorganic glue; their composition differs between core and shell; and even neighboring structural domains such as rod and interrod enamel are chemically and crystallographically distinct. These differences amount to only a few atomic percent, yet they strongly influence how enamel dissolves, wears, and resists damage.

We use imaging, microanalytical, and spectroscopic techniques to map the structure and composition of enamel across nine orders of magnitude in length scale and throughout its development, from an entire tooth down to individual atoms, and from the first deposition of the enamel matrix to fully mature enamel. We are now folding these measurements into computational models that aim to predict how enamel forms, matures, and dissolves under physiological conditions. This work frequently involves collaborators across the United States and around the world and contributes to a shared enamel atlas rather than remaining in a single laboratory’s drawer. Ultimately, we hope that understanding how enamel is built and deteriorates across scales will help us learn how to better protect, repair, and perhaps one day replace it.

Human enamel is remarkable: once it is formed, the cells that built it disappear, yet it can survive decades of mechanical and chemical challenges. At the same time, enamel cannot meaningfully regenerate after eruption. Our long-term goal is to understand how enamel acquires its extraordinary durability, how its structure and composition change during disease and aging, and how those changes influence dissolution and failure. Ultimately, we hope these insights will guide improved prevention, diagnostics, and future approaches to enamel repair or replacement.

Mineralized tissues are organic–inorganic composites that provide mechanical strength to an organism, helping it feed, move, defend itself, and even sense its environment. Their hierarchical architectures tolerate damage, resist fatigue, and can regenerate, remodel, or repair themselves. And they are made in water, near ambient temperature and pressure, from abundant ingredients, a route inherently more sustainable than the high-temperature processing we use to make ceramics.

The sea urchin embryo is an excellent model system for studying how an organism controls phase transformations. Its skeleton is two mirror-symmetric spicules of calcite (CaCO₃, as in limestone or chalk). Each spicule is a single crystal that curves and branches at closely controlled times and in precise crystallographic directions. Spicules from different species have distinct shapes, which suggests their growth is under genetic control. Each one is deposited by a small number of primary mesenchyme cells (PMCs) working so closely together that they fuse into a syncytium, sharing a single plasma membrane. The ability to shape the crystal may depend on the calcium carbonate arriving as a transient amorphous phase rather than crystallizing directly from solution.

What sets this system apart is that the PMCs keep working outside the embryo. That is rare enough among mineralizing cells to be worth a project in its own right. It means we can manipulate the process by genetic engineering or by providing molecular cues to the cells, and observe both cellular behavior and crystal growth in real time. This is what makes the long-term goal plausible: putting PMCs, or the molecules they depend on, to work making materials.

We use a broad range of techniques to get there. Cryo-electron tomography, STEM, and FIB/SEM tomography show us the cellular structures and the crystals themselves. Transcriptomics, proteomics, and recombinant antibodies tell us which molecules are present and where. Cell culture and in vitro experiments let us test what those molecules actually do. What we want to know is how specific proteins are assembled and patterned in the spicule matrix, and how that patterning sets nucleation kinetics and the direction the crystal grows. That is the first step towards porting the key players into a system that can be engineered and scaled using the tools of synthetic biology.

Sea urchins make masterful use of calcite throughout their lives. The embryo’s skeleton is only two single crystals; the adult’s test, spines, and teeth are orders of magnitude larger in volume and more complex in microstructure, composition, and function. We expect the design principles and the molecular toolkit to be shared. The embryo is where they are simplest to study, and what we learn there should show how skeletal elements arise from cellular processes across length scales, and how those processes shape crystal growth. That is a first step towards connecting developmental biology to the materials genome. The knowledge could reach areas as far apart as the programmed synthesis of bone grafts and the large-scale sequestration of carbon dioxide.

Acanthareans are marine, single-celled organisms that build an endoskeleton of celestine (SrSO₄). Three things about them are worth the attention. They grow their spicules as single crystals with shapes that are very different from those observed in lab-grown crystals, and those shapes are specific to the species. They remodel the skeleton, and even dissolve it, at defined points in the life cycle. And they select Sr²⁺ out of seawater in which Ca²⁺ is a hundred times more abundant.

Each individual has either ten diametral or twenty radial spicules. Shape, connectivity, and the architecture of the central junction that joins them differ markedly among the roughly 150 known species. Spicules are faceted in some, smoothly curving in others, and can carry barbs, wings, or branches that anastomose into regular lattices and porous plates. Aspect ratios reach twenty, where synthetic celestine grows as faceted tablets. In the few species examined so far, the long axis of the spicule runs parallel to the crystallographic a-axis. Form this consistent, and this specific to a species, is strong evidence that the process is under genetic control.

The form is not fixed within a single life either. Spicules grow more elaborate as an individual matures, and in some clades the endoskeleton is remodelled into a mineralized cyst before hundreds or thousands of flagellated swarmer cells are released. So the organism can reshape its crystals at different points in its development and dissolve them in a controlled way, which suggests genetic regulation here too, perhaps through overlapping or life-stage-specific sets of genes.

Seawater holds 88 µM Sr²⁺ against 10.5 mM Ca²⁺, and it is undersaturated with respect to celestine. Sulfate, at 28.9 mM, is not limiting. Because their ionic radii are similar, Ca²⁺ and Sr²⁺ are usually transported more or less indiscriminately by calcium channels and pumps, so most biominerals take up strontium at close to the ambient ratio. Acanthareans do not. How they manage it is unknown: the answer could lie in selective channels or pumps, or in holding the local sulfate concentration in the narrow range that precipitates celestine but none of the calcium sulfates.

The organic and inorganic biochemistry and physiology of acanthareans is largely unexplored. Our long-term goals are to identify the design principles used by acanthareans and apply them in bio-inspired materials and bio-enabled routes to capture Sr²⁺ in the presence of chemically similar ions. That ability matters directly for the efficient removal of ⁹⁰Sr, a highly active radioisotope present in nuclear fallout, in spent fuel rods, and in the high-level nuclear waste held at federal facilities. ⁹⁰Sr is dangerous precisely because nothing distinguishes it from calcium: a similar ionic radius and similar chemistry mean transport proteins take it up indiscriminately, so it accumulates in bone and teeth, where its beta decay, with a half-life of about 29 years, goes on delivering a dose for decades.

Many sea urchins graze on rocky reefs, frequently occupying pits they excavate themselves. They erode not only soft lime- and mudstone (Mohs 2 to 3) but substantially harder substrates, including sandstone and granite (Mohs 6 to 7). Their teeth, however, are composed largely of calcite (Mohs 3), softer than much of the substrate they cut. Sea urchins compensate through a strongly hierarchical, compositionally and functionally graded architecture, and through continuous growth.

Continuous growth means that every stage of tooth development is present in a single tooth at any one time. Odontoblasts arise in the plumula attached to the cervical end and fuse into a syncytium that deposits magnesian calcite (Ca_1-xMg_xCO₃). As the maturing tissue advances towards the incisal end, the syncytium withdraws, connecting the crystalline elements with widening mineral columns and ultimately yielding an acellular tissue. In effect, the bricks go down first and the mortar is filled in afterwards.

The tooth combines fibrous and platy elements that in combination confer wear resistance, toughness, and self-sharpening. These microstructural elements differ markedly in Mg content. Primary and secondary plates, among others, consist of high magnesian calcite (HMC), with up to 13 at% Mg on Ca lattice sites. The columns that connect the plates reach 35 at% Mg, far beyond the nominal solubility limit of Mg in calcite; we refer to this phase as very high magnesian calcite (VHMC).

Both HMC and VHMC are thermodynamically unstable under ambient conditions, and no ambient synthesis of VHMC is known. The strongly hydrated Mg²⁺ ion poisons calcite growth, so large single crystals of HMC or VHMC are difficult to obtain under mild solution conditions. Synthetic routes rely on elevated temperature and pressure and yield polycrystalline material with small grain sizes. Given the substantial increase in hardness on Mg substitution, and evidence of precipitation hardening in Mg-substituted calcites, there is considerable interest in how organisms achieve it. For this reason we are working to understand the mechanism by which sea urchins control Mg content far from equilibrium. Candidates are already in hand: comparing the proteome of the sea urchin tooth, which contains VHMC, with those of mineralized tissues that contain only HMC, Keith Alvares and co-workers identified a family of proline-alanine-rich phosphoproteins (PARPs).

Developmental, cellular, and physicochemical processes are inextricably linked in the biosynthesis of mineralized tissues, and biological control over phase transformations is an integral part of it. Properties and performance depend strongly on microstructure: the arrangement of inorganic and organic components, and the compositional gradients running through them. Understanding how cells pattern and maintain a privileged environment for mineral deposition, how they transport and modulate precursor concentrations, and what cellular machinery they use to control crystal growth across length scales is a prerequisite for intervening when developmental processes go awry, for engineering strategies to regrow and replace damaged tissue, and for designing bio-enabled and bio-inspired materials and processes. No hierarchical, functionally graded tissue of this kind is yet understood at that level. The availability of transgenic adult sea urchins now makes the tooth a tractable system in which to bring developmental and structural biology, biochemistry, and materials science to bear together.

Our research is transdisciplinary, drawing on materials science and engineering, chemistry, and the life sciences. Whichever of those you trained in, you will pick up skills from the others. The work runs from experiments at the bench, in core facilities at Northwestern and at our Chicagoland partners, and at national user facilities — the Advanced Photon Source, the Advanced Light Source, the Midwest Center for Cryo-Electron Tomography — through demanding data analysis and visualization to computational modeling. No single project needs all of it. Wherever possible, you will learn to run even the most sophisticated instruments yourself rather than hand samples to someone else.

Trainees who do well here

• are curious about how things really work.
• appreciate the beauty and complexity of the natural world and of living organisms.
• are eager to learn new skills, and to get good at them.
• are ready to take ownership of a project and lead where it goes.
• are ready to join a team and contribute to other people's projects.
• are keen to teach and mentor less experienced members, including undergraduates and interns.
• can see themselves working across disciplines, with collaborators trained very differently from themselves.

Postdocs should write directly with a CV and a letter covering what you have worked on, what you want to work on here, and why.

PhD students apply through the Materials Science and Engineering PhD program at Northwestern. The department receives more than 600 applications each cycle, and every one is vetted by the graduate admissions committee. Individual professors are much easier to reach once the committee has offered you a place in the department. When you do write, Derk generally replies only to inquiries that make clear why our field, and this lab in particular, appeal to you.

MS students also apply through Materials Science and Engineering. Once you are admitted, write to Derk to discuss projects for MSE 499 Independent Study or for the thesis-track MS.

Northwestern and Chicagoland undergraduates from any science or engineering background are welcome to write and ask about research opportunities.

Undergraduates at other US and international institutions should come through one of the Northwestern-run summer programs: the MRSEC REU, the IIN REU, SROP, or MICRO. We cannot host students from outside the US except through these or equivalent programs. Note that the MRSEC and IIN REU programs require US citizenship or permanent residency.

Interns from Chicagoland schools are welcome to write and ask what is currently available.

Where to write. Derk Joester, Northwestern University · d-joester@northwestern.edu