Clues to Alzheimer’s and ALS revealed in the physics of cells

Credit: John D. & Catherine T. MacArthur Foundation


Clifford Brangwynne, PhD, credits his start in science to Fritjof Capra’s popular science book, “The Tao of Physics” about the implications of quantum theory. That book—and a random ride home from his high school job at Barnes & Noble with an MIT graduate student in materials science—lit the spark.

“I was a late bloomer,” Brangwynne said. “I wasn't one of those kids with a chemistry set in my basement, competing on the math team and all of that.”

By his freshman year at Carnegie Mellon University, Brangwynne decided to take an introduction to materials science course. He remembers being enthralled during a lab activity pouring molten aluminum alloys at over 1,000°Celsius to study the crystallization process—and he’s been hooked ever since.

That introduction to materials science, paired with his fascination with cell biology, how cells function, and how they move, has led him to a stellar scientific career, evidenced most recently by being named the 2020 Blavatnik National Awards for Young Scientists Laureate in Life Sciences.

The Blavatnik Family Foundation and the New York Academy of Sciences announced all three 2020 Laureates in July. Brangwynne was also a Blavatnik National Awards Finalist in 2019 and 2018.

Clifford Brangwynne was honored as a Blavatnik National Awards Finalist at the 2019 Blavatnik National Awards ceremony

Clifford Brangwynne (front row, second from right) was honored as a National Awards Finalist at the 2019 Blavatnik National Awards Ceremony at the American Museum of Natural History

Now a biophysicist and bioengineer at Princeton University, Brangwynne, 42, was honored for his discovery of liquid-liquid phase separation as a cellular organizing principle. Cells typically separate the many biochemical reactions they perform by surrounding them in a membrane. In liquid-liquid phase separation, reactions are separated without a membrane into groupings called condensates, similar to tiny oil droplets that separate from vinegar in newly shaken salad dressing.

Without the restrictions of membranes, cells can benefit from the constant formation of new and different biochemical reactions. His studies suggest that when this process goes awry, cells can die and lead to medical conditions such as Alzheimer’s disease or ALS (amyotrophic lateral sclerosis).

"The recognition of this new field at the interface of cell biology and soft matter physics inspires my lab to continue breaking the barriers separating scientific disciplines," Brangwynne said.

Credit: John D. & Catherine T. MacArthur Foundation

The first Blavatnik National Awards Laureate from Princeton University, Brangwynne is a professor in the Department of Chemical and Biological Engineering. He also is an investigator at the Howard Hughes Medical Institute —one of the most sought-after appointments in biomedical research.

Before finding his footing in science and academia, Brangwynne thought that science would be a lonely profession. He grew up in Boston in what he said was a “large, wonderful” working-class family “full of electricians and plumbers and house painters and nurses.”

From that, he said, he had a misconception of an “isolated scientist, working alone” and never speaking to others. “I realize now that that was incredibly mistaken,” he said, describing his work as social, interesting, and multidimensional.

He compared running his lab to a team sport, allowing him to interact with students and scientists across different areas of expertise.

Credit: John D. & Catherine T. MacArthur Foundation

Outside the lab, he enjoys reading about history and spending time with his family of five.

Brangwynne said his several mentors fueled his passion and pushed him to follow his scientific instincts. The greatest piece of advice he has ever received? "Do what you love and the rest will take care of itself."