SU research team blazes new trails in emerging field of nanobiotechnology

SU research team blazes new trails in emerging field of nanobiotechnologyJanuary 29, 2009Judy Holmesjlholmes@syr.edu

Biologists have long known that proteins, which are essential to all life processes, are able to freely move through the cell membrane in a process called protein translocation. What’s not clearly understood is exactly how cells import and export these relatively large protein molecules without expending a lot of energy. The process is akin to running a marathon uphill without breaking a sweat.

Answers to this biological puzzle are coming from a relatively new field of research in nanobiotechnology, a multidisciplinary field in which a research team in the Department of Physics in Syracuse University’s College of Arts and Sciences is making important contributions. The team’s findings may someday lead to new ways to detect and treat diseases.

“The keyword is nanopores,” says SU biophysicist Liviu Movileanu. “Nanopores are the elements that bring the scientific disciplines together.”

Nanopores-which are about 20 times larger than an atom (a trillion could fit on the head of a pin)-are perfect devices through which small and large protein molecules are transported across the cell membrane. Movileanu’s team has demonstrated that movement through these tiny biological tunnels seems to be governed by the fundamental laws of physics, first described during the 18th century.

In a groundbreaking study published last spring in the Journal of the American Chemical Society, Movileanu and his colleagues at SU and Northwestern University discovered that proteins are pulled, one molecule at a time, through a nanopore by electrostatic interactions between positive charges on the translocating protein and negative charges the researchers placed within the nanopore. It’s the same type of electrostatic force that causes a balloon to stick to a child’s hair, and which was first studied in detail by French physicist Charles Coulomb around 1784.

“The physics turns out to be quite simple,” Movileanu says. “But the biology is much more complex. However, we can’t understand complex biological systems if we don’t first understand their physics.”

In addition to studying the physics of nanopores, Movileanu and his research team are trying to gain a better understanding of nanopores from a biological perspective. Their experiments defy description-is it physics, chemistry or biology? Turns out, no one is quite sure.

“The work we do is not what you would typically find in a physics research lab,” Movileanu says. “We create organic molecules, extract genes, re-engineer proteins and drill silicon-based materials at nanometer-scale resolution. By combining what nature has created with new technologies, we are able to do some pretty powerful experiments.”

Both the National Science Foundation and the National Institutes of Health are supporting Movileanu’s work. His eclectic team includes scientists and doctoral students with skills in molecular biology, biochemistry, engineering and physics.

“Nanopores are an essential path for cells to exchange materials,” says team member Mohammad Mohammad, a postdoctoral research associate who earned a Ph.D in biochemistry and molecular biology at Texas A&M University. “By studying their function in nature, we might be able to manipulate the natural process and create new pathways into cells for drug delivery or create new diagnostic tools.”

When a protein molecule is pulled through a nanopore, the tiny electrical current that flows through the nanopore changes. The nature of the current change is unique to the properties of the molecule moving through the nanopore, a characteristic that makes nanopores a potentially powerful tool for scientists.

“Nanopores provide us with a new single-molecule tool-a new window-through which we can study the dynamic properties of individual protein molecules and their subtle interactions with each other,” Movileanu says.

In a series of experiments led by Khalil Howard, a Ph.D. student in SU’s Structural Biology, Biochemistry and Biophysics (SB3) Program, the researchers genetically modified a nanopore by conferring properties onto it that are not found in nature. The new nanopore was more stable than the original, and the modification created a sensor element in the nanopore that could be used to detect a variety of protein or nucleic acids and their interactions. This kind of biological sensor may one day be used to detect diseases at very early stages.

David Niedzwiecki, a physics Ph.D. student, is studying solid-state or non-biological nanopores in collaboration with John Grazul, co-manager of the Electron and Optical Microscopy Facility in the Cornell Center for Materials Research. Researchers believe that solid-state nanopores, which are made of silicone nitride, could be more stable and predictable than protein nanopores and may also provide an alternative material for building biological sensors.

“The field of nanobiotechnology is rapidly expanding all across the country,” Movileanu says. “Even a failed experiment is half of a success. Some of the best discoveries are made when an experiment deviates from what was anticipated. If it didn’t happen that way, science would be boring.”