He noted that bone fracture is an extremely serious problem for elderly people, especially those with osteoporosis. Bone fracture is one of the leading factors in decreasing quality of life for the elderly.
“Cancer and heart disease can kill you but bone fracture and arthritis make you miserable,” he said. “Once a serious bone fracture occurs, then quality of life goes down. Less than one-third of elderly women who have a hip fracture return to previous function. Both bone fracture and fear of bone fracture cause elderly people to limit their activities. More women die within a year of hip fracture than die after a heart attack. So it’s a very serious problem and a lot of work has been done to develop good diagnostics. The leading diagnostic is bone mineral density.”
Measuring bone mineral density is valuable because it reveals how much bone mineral a person has left, he explained. An individual’s bone mineral density peaks around age 30, then decreases for the rest of his or her life. By the time the person becomes elderly, very serious bone loss may have occurred.
“As if this weren’t bad enough, it is also true that the materials properties of the bone decrease with age,” said Hansma. “Not only is there less bone, but what exists is less fracture resistant. The cause of this is not well understood. Our research is aimed at understanding that.”
Hansma noted that bone has been studied extensively since Galileo. “Galileo wrote a really nice paper about bone, showing why elephants need bones that are wider relative to their length than small animals,” said Hansma. “Over 20,000 scientific articles per year are written about bone. But although bone is extensively studied, little is known about how it works at the molecular level. Our study is the beginning research on this.”
The glue that the scientists found appears to contain “springs” that uncoil when the bone is stressed, helping the bone to absorb shock. When the stress is relaxed, they coil back to their original structure. The discovery is of a self-healing protective mechanism that prevents the separation of the bone’s protein fibers or fibrils.
The possible implications for human health are important, explained Georg E. Fantner, a UCSB doctoral student in physics and a key player in the bone research. “The findings may lead to therapy for bone fracture, or even to prevention,” he said.
Working in Hansma’s physics lab, in collaboration with the UCSB labs of Daniel E. Morse, professor in the Department of Molecular, Cellular and Developmental Biology, and director of UCSB’s Institute for Collaborative Biotechnologies, and Galen D. Stucky, professor of chemistry, the interdisciplinary group of scientists spent several years tracking down where the glue was located in bone, and how it worked.
Interdisciplinary research is fast becoming a hallmark of scientific research at UCSB. “This work couldn’t have been performed without the interdisciplinary collaboration that we have,” said Hansma. “This is not just talked about at UCSB, we actually have weekly interdisciplinary meetings.” In addition to the professors mentioned above, Herbert J. Waite, professor of molecular, cellular and developmental biology, and Frank Zok, professor of materials, attend these meetings. “And it’s not just professors collaborating, but many students are involved, performing a wider range of measurements than would be available to any one researcher. For example, James Weaver, a graduate student in Morse’s lab, took the spectacular three dimensional images now on my office wall with an electron microscope in their lab.”
Hansma explained that at many excellent schools it is more typical for a professor to do all of the research in his or her own lab. “These schools place value on self-sufficiency and doing it all oneself,” he said. “At UCSB many of us choose to work differently, because there’s a big difference between a physicist who has read a lot of papers involving biochemistry, and a real biochemist. The biochemist has a depth of experience that a physicist could never hope to achieve, and will bring fresh perspectives to the work. The same is true for chemists, engineers, and materials researchers. We have joint interests and we also help each other on personal interests.”
Another student who contributed to the bone work from Morse’s lab is Bonnie Bosma. She performed gel electrophoresis on glue candidates. This is a process where macromolecules are separated on the basis of their electrical charge and size.
“Before this research, it was well-known that the mechanical properties of bone depended on mineral particles and on collagen fibrils,” said Hansma. “The picture of bone was that it consisted of these collagen fibrils coated with tiny mineral crystals only a few atoms thick. What we found is that there is glue in bone that holds these mineralized collagen fibrils together, and this glue works along the same principles that our interdisciplinary research group found in abalone shells. This glue involves sacrificial bonds (with hidden length) that uncoil when the bone is stressed.” That interdisciplinary research group included the research groups of Morse and Stucky, as well as that of Herbert Waite.
“It’s especially exciting for us to find the profound medical significance of our discoveries for human bone,” said Daniel Morse.
Morse described the discovery of “molecular shock absorbers” providing a kind of self-healing glue holding biological mineralized structures together when studying the abalone shell six years ago. “It’s truly remarkable to find the same fundamental mechanisms operating in bone,” said Morse.
He noted that these mechanisms give young healthy bone its tremendous resiliency and resistance to fracture, and actually help heal some microcracking soon after it has formed. “We’re especially interested in learning how these molecules change and become depleted with age as well as in certain diseases,” said Morse. “A potential benefit from these discoveries is the prospect that we might now learn how to protect bone from these deleterious changes, and perhaps actually reverse some of the changes.”

Hansma explained, “The thing that’s exciting about this research is that we’ve identified a mechanically important component of bone.” When the exact molecules are identified, these can then become therapeutic targets, for example, in diet, or drug therapy. He said the group has made a fundamental discovery of something that’s important for bone fracture resistance that was previously unknown. Now its degradation mechanisms and deficiencies can be studied. “If you don’t know something is important then you can’t do anything about it. This is a fundamental and new discovery in an old and well-studied field.”
Hansma and his colleagues at UCSB have pioneered the use of the atomic force microscope (AFM) in looking at the nano-scale level of biological materials –– that is, down to a billionth of a meter. His contributions to the development of biological scanning probe microscopy and for the molecular resolution imaging of biological molecules in aqueous solutions are known worldwide. His group built a series of AFMs that served as prototypes for commercially successful AFMs developed and marketed by Digital Instruments, a Santa Barbara company. With the research group of his former wife, biophysicist Helen Hansma, the scientists shed light on how proteins fold correctly into the three dimensional shapes that they need to function. Hansma and his group also invented the Scanning Ion Conductance Microscope, which can measure ion conductance through pores in membranes.
Hansma’s research began with inelastic electron tunneling and scanning tunneling microscopes and evolved to the development of AFMs. He is particularly interested in developing AFM applications for biology and medicine. In 1989, Hansma’s team succeeded in observing the blood-clotting process within blood cells. Before the use of the AFM, it was impossible to see these tiny molecular structures that make up the process.
“My first love is building things,” said Hansma. “We first started with the AFM in 1986. I believe my most important achievement in technology development has been the development of practical scanning microscopes, especially AFMs, for operation in air or fluids. I work in Broida Hall, named after Herb Broida, who was a very active experimentalist and a great mentor for me. The saying of his that has helped me the most was ‘you should do every experiment as poorly as possible’ to innovate. A different version of this same basic teaching is Buckminster Fuller’s statement that the key to innovation is to ‘make as many mistakes as possible, as rapidly as possible,’ and, of course, to learn from each one.”
He explained that these two teachings were enormously useful in building microscopes. “We know that we can never build the perfect microscope on the first try, so instead we work to build something quickly,” he said. “We then try it, find out what the problems are, and –– this is a key point –– the problems are often not what we anticipated. Then, we attempt to solve the problems we find in the first prototype with a second prototype and then the problems we find in the second prototype with a third prototype. And so on. It usually takes us many prototypes to get to something that satisfies us. For us, the path is always unexpected. If we knew where we would end up, we’d start there!”

The AFM uses a cantilever tip, much like a needle on a phonograph, to scan the surface of the material being tested and to create a type of topographic map of the material. The tip is also used to stretch molecules to see how they break down and this measures their response to tension.
“In 1995 we continued with AFM development by beginning work on a new generation of AFMs based on small cantilevers,” said Hansma. “Our very first atomic force microscopes used home built cantilevers on which we glued diamond tips by using eyebrow hairs to apply epoxy and transfer shards of shattered diamonds. Fortunately, before our eyebrows ran out, Calvin Quate’s group at Stanford University developed microfabricated cantilevers with integrated tips. The fundamental reason these cantilevers worked better was that they were smaller.”
Hansma explained that his bone research began with him breaking bones with sledgehammers in his garage. He boiled and then baked a soup bone from the grocery store. “I saw that the bone grew more brittle as I baked it to degrade the organic material. By the time the bone was baked a lot it was really brittle. I started doing this sledgehammer work in the summer of 2003 after I had seen there was glue in the bone from AFM experiments.”
Next, Hansma enlisted the help of Kirk Fields, associate development engineer, to help with the design of a machine with a force cell to monitor the impacts on the bone. “I used the force cell to make the bone break in the same way it would when a person falls down. Then I went to the other end to get a complete picture of how bone fractures by using the AFM.”
Working with his hands in his garage is one way that Hansma taps into his creativity, his scientific imagination. “By actually working with my hands and making crude prototypes, I get ideas about how to refine them. As I’m screwing in hinges or sawing, I have time to think.”
The research group is now working on high-speed, easy-to-use AFMs for biomedical imaging. And over the Christmas holidays in 2004, Hansma built a crude bone diagnostic instrument, again in his garage, for testing bone material properties in patients. Although it is still in the experimental stages, two physicians want to do clinical tests on the instrument already.
In addition to those mentioned above, collaborators on the path-breaking bone research include Johannes H. Kindt, Philipp J. Thurner, Georg Schitter, Patricia J. Turner, Blake Erickson, Zachary Schriock and Simcha Frieda Udwin of the Hansma lab, and group alumni Jacqueline A. Cutroni, Tue Hassenkam (now of the Nanoscience Center, Copenhagen University) and Geraldo A. G. Cidade (who has recently moved to the Biophysics Institute Carlos Chagas Filho at the Federal University of Rio de Janeiro, Brazil). Chenjun in Waite’s lab contributed, as did Leonid Pechenik, a postdoctoral scholar at UCSB Physics.
Hansma earned a Ph.D. in physics at UC Berkeley and has been a member of the faculty at UCSB since 1972. He holds twenty one U.S. patents –– these include Scanning Probe Microscopy as well as a new generation of AFMs. He has written 315 scientific articles and has been awarded many honors including the Biological Physics Prize from the American Physical Society, one of the highest honors a physicist can receive.