Biomedical engineering associate professor Jeanne Stachowiak received the 2023 Michael and Kate Bárány Award for her paradigm-shifting discovery in the field of membrane biophysics.
by Josh Kleinstreuer
Her research details how cells control the shape and content of their membranes.
Membrane curvature is critical to many cellular processes, including the internalization of signaling receptors and key nutrient transportation. The bottom line: if a cellular membrane is damaged or not functioning properly, the cell will die.
“Membrane curvature is required for the life of every cell. It also provides a mechanism for pathogens, such as viruses, as well as nutrients and drugs to enter cells. Therefore, understanding the fundamental mechanisms responsible for membrane curvature is critical to the understanding of all diseases,” said Stachowiak.
the research:
The prevailing view that is structured protein motifs such as amphipathic helices, or crescent-shaped BAR domains, are the drivers of membrane curvature.
For the most part, scientists ignore disordered proteins in the context of membrane bending because they lack a defined structure. Stachowiak and her team demonstrated that these disordered domains are more efficient at driving curvature than traditional domains due to the amount of space they occupy.
Stachowiak’s research demonstrates that proteins can induce membrane curvature solely through a surface-crowding mechanism. More importantly, the results show that membrane-bound protein domains induce membrane curvature without hydrophobic insertion.
When proteins bind to the surface of the membrane, the area that each protein can explore decreases as the density of proteins on the surface grows. This causes pressure that simultaneously increases with the membrane protein coverage.
Figure 1: Crowding among membrane-bound proteins generate steric pressure, driving the membrane to bend.
At sufficiently high coverage, the pressure can overcome the energetic cost of membrane bending which increases the area where proteins diffuse. Stachowiak’s research predicts that a 20% to 50% range of protein coverage on tubulated membranes is sufficient to drive the formation of highly curved membrane structures through protein–protein crowding. The data suggests proteins with high membrane affinity have the greatest capacity for curvature generation.
Stachowiak emphasized the group effort that is involved with academic advancements and discoveries.
stachowiak’s team: Back row (left to right): Susovan Sarkar, Sadhana Gollapudi, Yohan Lee, Brandon Malady, Feng Yuan, Grant Ashby, Ketsia Zinga, Caleb Walker, Arjun Sangani, Carl Hayden, Advika Kamatar.
“Nothing significant happens in science without a team. I am grateful to the team I worked with when we first discovered the protein crowding mechanism: Eva Schmid, Carl Hayden, Darryl Sasaki, and Dan Fletcher,” Stachowiak said. “I am also grateful to all my wonderful lab members who have helped me build on that finding over the past decade. Finally, I am grateful to my husband, Tim, who has partnered with me to raise our family while we both pursued our passions at work.”
The award:
The Biophysical Society honored Stachowiak at its 67th annual meeting in San Diego this year. The Society’s president, Gail Robertson of the University of Wisconsin-Madison, said Stachowiak established herself as a leader in the area of membrane shaping, and the organization is excited to follow her career and future achievements.
For Stachowiak, the excitement about her work matters most.
“I am honored that my colleagues find my lab’s work to be important and interesting. That means more to me than any award ever could,” she said.
The Michael and Kate Bárány Award for Young Investigators recognizes outstanding contributions to biophysics by a person who has not achieved the rank of full professor at the time of nomination. In recognition of the endowment gift from Michael and Kate Bárány, the award was renamed in 1998.
|