By Calla Cofield
A pioneering network of physicists, engineers and biologists are beginning to develop a picture of the cell as a mechanical device, not just a chemical one. As a result, scientists are gaining new insight into the structure, behavior and functions of the cell, as well as its malfunctions and failures. This new map of the tiny, yet complex structures will change the treatment of diseases that originate in or affect them. But within this scientific community (so new that it hasn’t settled on a name for itself) there has arisen some debate about how soon this research will result in disease treatment.
“Cells don’t just speak through chemistry, they speak through forces,” said Alex Levine at a press conference on cell mechanics at the APS 2010 March Meeting in Portland. Levine, Associate Professor of Chemistry and Biochemistry at UCLA, is suggesting that understanding the chemical nature of cells is only half the story.
For hundreds of years, biologists have found hints about the mechanical nature of cells, but a lack of sufficient tools always halted further investigations. In the last two decades, technological advances have opened the door for researchers, particularly physicists and engineers, to study the nanoscale forces exerted by cells and the atomic structure of the materials that make them up. Almost overnight, scientists have become aware that cells may change their shape based on directional blood flow, or migrate from one area to another in order to find the environment with the right rigidity for development. Cells may communicate internally by changing the tension in connecting fibers. Chemical cues may cause a cell to change the equilibrium point of a mechanical system in order to generate motion, such as tensing muscles.
Trained as a physicist, Levine entered the field of biological physics via the study of polymers. Cell cytoskeletons are made of a polymer unlike anything artificially created in a lab, and they represent one of the many arenas where the study of cells offers the promise of new physics. Now Levine has taken a particular interest in what he calls “cell quakes” or tremors in the cell wall that help the cell move around.
“We’re in sort of a Lewis and Clark phase in the field,” said Levine, “a time when you can discover mountain ranges and rivers. There’s a lot of low hanging fruit.”
Much higher up the tree, dangling above the heads of researchers, is the promise of utilizing this new understanding of the cell to treat and cure disease. And Denis Wirtz has wasted no time going after that highly coveted and direly needed prize.
Wirtz was trained as a physicist and chemical engineer, but upon entering an appointment in Chemical Engineering at Johns Hopkins University, he dove head first into biology. In 2008 and 2009 he and his research group published work showing that cells from mice suffering from accelerated aging (progeria) and muscular dystrophy, two diseases that originate from different locations on the genome, display the same kind of physical deformation to critical structures in the cell. Whether the deformation is the cause of the disease or a clue to its source is uncertain, but Wirtz is encouraged that he’s on the right track.
Without so much as a pause, Wirtz is now ready to tackle one of the most deadly and dreaded diseases in America: cancer. In November 2009 the National Cancer Institute officially opened the Engineering in Oncology Center (EOC) at Johns Hopkins, where Wirtz will serve as director. The NCI invested 14.8 million dollars over five years in the EOC, one of twelve in the country. A press release from Hopkins says the Center will give the participating cancer researchers a “fresh pair of eyes” by teaming them up with physicists and engineers who have not specialized in cancer research, or in some cases even biology.
“Little is known about the effect of mechanical forces on the regulation of cancer cell growth,” said Wirtz in the Johns Hopkins press release. “That is what the Engineering in Oncology Center and the National Cancer Institute want to find out. The results should point us to therapies and diagnostic tools that complement existing genetic or molecular treatments.”
Wirtz talks passionately about his interest in understanding the science of cancer, and his hopes for treating it. At the APS Meeting in Portland he emphasized the important role that physicists and engineers will play in reaching that goal.
On the other hand, some of Wirtz’s colleagues, including Levine, have cautioned against being overly optimistic.
“Medicine is the engineering application of physics and biophysics,” Levine said. “As you know, there was a long time between the beginning of quantum mechanics and the production of transistor radios. Personally I think this is an even more complicated subject. I suspect there will be a long timeline between treatments and the biophysics we are doing.”
However, neither Levine nor other members of the field think that Wirtz’s work will yield no positive results. Paul Janmey, a professor of physiology at the Institute for Medicine and Engineering at the University of Pennsylvania, adds that research institutes like the EOC may make new breakthroughs in cancer diagnostics.
“It’s plausible that we’ll be able to identify tissue more prone to full blown tumors,” Janmey said. “Chemical signs that tissue will become cancerous haven’t been particularly successful. If there is a relatively non-invasive, micromechanical way to identify local stiffness and boundaries between soft and hard tissues that look similar, then that could be a strong indicator of where tumors will develop.”
With the potential for great disappointment and frustration, there is an argument for keeping one’s hopes restrained. At the same time, the high stakes also call for the immediate pursuit of solutions. “If [Wirtz] is right,” adds Levine, “All the better.”
Together at the APS Meeting, Levine and Wirtz have the rapport of old friends, and they jointly discussed topics with reporters. More important than their individual pursuits is advertising this new field to physicists, who, they can both agree, will play a crucial role in its progress.
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