Researchers Discover New Mechanism for Membrane Curvature Sensing

researchers discover new mechanism for membrane curvature sensing

Wade Zeno, a postdoctoral fellow working with Dr. Jeanne Stachowiak, was the lead author on a new paper in Nature Communications that sheds light on a previously unknown mechanism for membrane curvature sensing.

Researchers from the Department of Biomedical Engineering and the Department of Chemistry at The University of Texas at Austin have discovered a new mechanism of membrane curvature sensing by proteins that lack a defined structure. Understanding this first step in membrane trafficking will allow researchers to better understand how cells work and ultimately how to treat disease. The team, led by Associate Professor Jeanne Stachowiak and Professor Dave Thirumalai, recently published a paper on the finding in Nature Communications.

The paper’s first author, postdoctoral fellow Wade Zeno, and others were able to demonstrate that intrinsically disordered proteins, which are floppy proteins that lack a well-defined shape, prefer to bind to highly curved membranes because doing so allows them to maximize their entropy, or lack of order.

“Imagine dumping a bag of blue marbles on the ground, and then a bag of red marbles,” says Zeno. “Without interference, these marbles would be mixed heterogeneously. Essentially, disordered proteins behave the same way. It takes more energy for them to become ordered, so they prefer to bind to curved membranes, which allow them to remain more disordered.”

Stachowiak’s lab focuses on understanding the molecular-level mechanics of cell behavior. Understanding how the cell behaves fundamentally may ultimately help researchers gain insights into disease treatment. Membrane curvature sensing is important because it’s the first step in membrane trafficking in cells. Membrane trafficking includes all of the processes by which cells use membrane-bound compartments to transport proteins and other molecules within the cell. Malfunctions in membrane trafficking contribute to a variety of diseases, such as cystic fibrosis, diabetes, or even cancer.

Acquiring a fundamental understanding of how proteins regulate membrane traffic is a crucial step in deciphering and combating disease.

Monte Carlo simulations, performed by Dr. Upayan Baul from Professor Thirumalai’s lab, were used to interpret the experimental data and pinpoint the entropic nature of the curvature sensing mechanism.

This research was funded by the National Institutes of Health through R01GM120549 to Stachowiak, the National Science Foundation through CHE 16-36424 to Thirumalai and by the Collie-Welch Chair through F-0019 to Thirumalai.