Christopher Jarzynski Sees a Big Future for Small Machines

So far in 2020, he was elected to the National Academy of Sciences and awarded Simons and Guggenheim Fellowships. 

Most people tend to think of a machine as something large and bulky with mechanical gears and a roaring engine. But when Christopher Jarzynski thinks of a machine, he thinks small. Very, very small.

Jarzynski—who was elected to the National Academy of Sciences last month—studies how the laws of thermodynamics, which were first established to explain how steam engines work, apply to molecule-sized machines. A few decades ago, scientists began to recognize that certain molecules in living cells can be thought of as microscopic machines, because like all machines, they carry out work. They convert sugar into energy, shuttle material from one place to another, flip switches, build amino acids into proteins, create heat and much more.

“At some level, it seems that the same concepts used to talk about work and energy exchange in large-scale systems, such as a steam engine, should apply to these very, very small systems such as bio-molecular machines,” said Jarzynski, a Distinguished University Professor in the Department of Chemistry and Biochemistry. “But the question of how thermodynamic laws apply, or how they might need to be reformulated for very small systems, hasn’t really been explored that much until relatively recently.”

Part of what makes measuring energy at super-small scales so tricky is that, typically, calculations of energy in a system account for the heat that system generates. But heat is a measure of molecular motion, so if the entire machine is the size of a molecule or even smaller, you have to look at heat differently.

At the macroscopic level, understanding the laws of thermodynamics have enabled many modern technological advances—from jet engine design to refrigerator efficiency and a host of applications that were unimaginable when steam engines first hit the scene more than 300 years ago.

As researchers develop new nanoscale technologies, understanding thermodynamics at the molecular scale is going to be just as important. For example, thermodynamics play a role in knowing how well a potential drug molecule binds to its target or how a single-cell organism performs information-processing tasks such as deciding to move toward a food source. Understanding the details of how these processes work may help guide the development of artificial molecular machines that similarly can process information.

And Jarzynski’s research is laying the groundwork for those types of advances. He gained notoriety early in his career when he developed a now-famous equation that bears his name. The Jarzynski equality is considered a fundamental law of statistical mechanics—an area of study that investigates how macroscopic observations such as temperature and pressure are related to what happens at the microscopic level.

Jarzynski’s equation shows that the free energy—the energy available to do work—in a molecular-scale system can be determined by measuring the amount of work it takes to go from one equilibrium state to another, even if the system does not remain in equilibrium during the process. This was a major breakthrough, because previous approaches to measuring free energy at this scale required the system to remain in an equilibrium state, which is difficult, if not impossible, to achieve. The original 1997 paper that introduced the Jarzynski equality has been cited in the scientific literature over 4,000 times.

The first experimental test of the Jarzynski equality involved the use of optical tweezers, which use laser beams to manipulate extremely small objects like biological molecules. When the inventors of optical tweezers won the Noble Prize in 2018, the Nobel Committee for Physics noted the Jarzynski equality as an important example of an application of the invention.

Jarzynski’s research has earned him recent guest lectureships at the Ludwig-Maximilians-Universität in Munich, the University of Chicago and the Tata Institute of Fundamental Research in India. He also won the American Physical Society’s 2019 Lars Onsager Prize, which recognizes outstanding research in theoretical statistical physics.

Most recently, Jarzynski was awarded a Simons Fellowship and a Guggenheim Fellowship, followed by his election to the National Academy of Sciences.

Although Jarzynski’s tenure home is the Department of Chemistry and Biochemistry, he was trained as a physicist. He earned his B.A. in physics from Princeton University and his Ph.D. in physics from the University of California, Berkeley. His research hovers at the boundary between two disciplines. Thermodynamics may be an area of physics, but molecular machinery—where proteins are folded and chemicals are built—lives in the realm of chemistry.

“When I would go to conferences, I found that I was interacting as much with chemists as with physicists. So, my research brought me to this very interdisciplinary place,” said Jarzynski, who holds joint appointments in the university’s Department of Physics and Institute for Physical Science and Technology.

His research was not always so interdisciplinary, though. In graduate school, Jarzynski focused on the physics of chaos theory, and he expected to continue studying chaos, particularly quantum chaos, throughout his career. But during a postdoctoral fellowship at the Institute for Nuclear Theory at the University of Washington in Seattle, Jarzynski met theoretical chemist William P. Reinhardt. The two men met regularly for lunch, and one day Reinhardt suggested a research topic he thought Jarzynski might find interesting.

“The topic was essentially how to use computer simulations to estimate free energy differences in complex molecular systems,” Jarzynski said. “And I’ve basically been working on that topic in some form or another for the last 20 years.”

After his postdoc, Jarzynski spent 10 years at Los Alamos National Laboratory. When he was offered a faculty position in the Department of Chemistry and Biochemistry at UMD, he was eager to make the shift to academia.

“I always wanted to end up at a university,” Jarzynski said. “I wanted to be able to teach and to build my own research group. I get excited about the science. And it’s rewarding to be able to convey part of that excitement to a class of students.”

Jarzynski teaches general chemistry and introductory physical chemistry to undergraduates, and he teaches a graduate course he developed that introduces students to non-equilibrium statistical physics.

On a high shelf in his office, nine champagne bottles stand in honor of the graduate students who earned their doctorates under his mentorship. He expects those bottles to be joined soon by three more for doctoral students he currently advises through UMD’s graduate programs in physics, chemical physics and biophysics.

“Being involved with the next generation of researchers has been one of the most rewarding parts of my career,” he said. “Typically, graduate students have not had that much research experience when they first come here, and it’s extremely fulfilling to see them interact with other group members, begin to own the work and transform into independent researchers.”

Jarzynski proudly watches his mentees enter the field to seek out their own successes. It’s not difficult to imagine them forging new ground in technological advances such as artificial molecular machines or even quantum-scale machines. When they do, they will build on foundations Jarzynski has been helping to lay since he was in their shoes.

Written by Kimbra Cutlip