Our bodies are made up of an array of materials. Beyond the organic flesh and blood that first come to mind lie the inorganic crystalline-based mineral structures whose placement is strictly controlled by biological mechanisms. We take for granted that teeth will grow exclusively in our mouths. We expect bones to form according to a predetermined placement of skeletal structure within our bodies and not in other areas of our anatomy. How do our bodies contain and control the growth of these crystalline materials? What causes the process to go awry and cause disease?
These are some of the questions Lara A. Estroff, Materials Science and Engineering, wants to answer. Estroff studies crystals, particularly biomineralization, the process by which living organisms produce minerals and control their growth to create teeth, bones, shells, external spines, and other materials.
“Biomineralization is where you can see molecular scale events translated up to the macroscopic level,” she says. “I can hold the crystals, shells, and bones, and they all have physical properties that trace back to these molecular level events. By studying how organisms grow their crystals, we can apply those ideas in the lab.”
How Crystals Grow in the Body
One lesson the Estroff Group has learned from biology is that often these crystals grow in special spaces within the organism’s body. “The crystals are not growing willy nilly anywhere in the organism, but rather the organism uses biological macromolecules to define a space in which they grow,” Estroff explains. “Often the space is quite small—only microns in size.”
The researchers are developing synthetic methods for achieving confinement in the lab, then studying the crystals they are able to grow. “In particular, confinement can be used to play some pretty funny tricks, getting crystals to incorporate impurities they wouldn’t ordinarily include in their structure,” Estroff says. “The impurities modify the properties of the resulting crystal. For example, by incorporating organic polymers, we can actually harden crystals, which are usually quite brittle.”
“The crystals are not growing willy nilly anywhere in the organism, but rather the organism uses biological macromolecules to define a space in which they grow.”
The Estroff Group is currently investigating ways to modify optical and electronic properties of crystals by combining materials that wouldn’t ordinarily commingle, for instance, a metallic material combined with one that is a semiconductor. These types of materials show promise for photo voltaic or catalytic applications. To facilitate her research, Estroff took a sabbatical a couple of years ago and visited the Lawrence Berkeley National Laboratory in California to learn how to apply very high resolution atomic force microscopy (AFM) to track crystal growth. Since then, she has set up an AFM microscope in her own lab. “Now we can track how crystal growth changes when we put these additives into crystals,” she says. “It gives us an edge. Not many groups are able to do this type of real-time imaging.”
Breast Tumors and Microcalcification
This more physical science aspect of Estroff’s research stays close to her roots as a trained chemist, but she and her lab also pursue research connected to biomedical problems. Over the past 10 years, they have begun a series of collaborations with colleagues in biomedical engineering. In one project with Claudia Fischbach, Biomedical Engineering, they are looking at the formation of microcalcifications in breast tumors. Microcalcifications are what mammograms detect, and they are extremely useful diagnostically to pinpoint breast tumors. However, after the initial diagnosis, they are not further utilized.
Estroff, Fischbach, and their collaborators are investigating the chemical composition and crystal structure of these breast tumor microcalcifications in an effort to understand their implications. Initially, they used frozen samples of breast tumors from Memorial Sloan Kettering Hospital in New York City, but recently they started a new collaboration with Cayuga Medical Center (CMC) in Ithaca, New York, where Cornell University is located. CMC will provide them with the fresh tissue samples they need for some of their techniques.
“With these fresh samples, we’re very excited about the possibility of getting more information out of the microcalcifications,” Estroff says. “In our initial studies, we found that all microcalcifications are not the same. By looking at their chemistry, we’re hoping to gain insight into how they are formed. Do they come before the cancer or after it? If they come after the cancer, can we learn something about the severity of the disease from them? We’re also interested in why breast cancer metastasizes to bone. Is the presence of these microcalcifications linked to that metastasis?”
Aortic Valve Disease and Calcification
Another disease associated with calcium is calcific aortic valve disease, in which the heart valve begins to calcify. Estroff has joined with Jonathan T. Butcher, Biomedical Engineering, and Eve L. Donnelly, Materials Science and Engineering, to look at the triggers that cause calcium to form in the heart valve, as well as to identify any interventions that can slow or prevent that mineralization.
“It’s a different set of questions from the breast cancer project because the calcification breaks down the function of the heart valve,” says Estroff. “We’ve taken a material science approach of characterizing both the mineral and the organic material surrounding it to see if we can learn what’s gone wrong. Is it just that bone is forming where it shouldn’t? Or is this a new process that’s not related to bone formation?”
Bone, Soft Tissue, and the Meniscus
In a third biomedical project, Estroff is collaborating with Lawrence Bonassar, Biomedical Engineering, to investigate the interface between bone and soft tissue represented by the meniscus, a specialized cartilage shock absorber in the knee.
“We want to understand how the meniscus works,” Estroff says. “There’s collagen in your bones and in the cartilage that makes up the meniscus. So the organic component is the same in both tissues, but mineral only forms in your bones, not in your cartilage. We want to understand how, in a very short distance of around a hundred microns, our bodies can move from full mineralization to no mineral at all. Controlling that mineral growth is not easy.”
How an Interest in Chemistry and Archaeology Led to Materials Science
As a child, Estroff was determined to become a naturalist like Jane Goodall. Then she discovered an affinity for chemistry and chose to major in it. Her undergraduate minor, though, was archeology. While pursuing research with the Weizmann Institute of Science in Israel conducting infrared spectroscopy analysis of plant remains at archeological digs, she was introduced to biomineralization.
“I became hooked,” she says. “I couldn’t stop thinking about it. Through biomineralization, I came back to the naturalist side of things. Now I can have my demo box full of teeth, bones, shells, and crystals.”