Tracking the movement of protein nanorods
A better understanding of protein movement can facilitate the design of advanced materials
Biological materials such as bones, teeth and shells are extremely durable. Their strength comes from their composition, which consists of a mixture of hard rock-like minerals and resilient carbon-based compounds such as proteins. Materials scientists are inspired by biological materials to develop a new generation of advanced materials based on proteins and minerals. However, scientists must first know how proteins attach and assemble on mineral surfaces.
Proteins are a key type of large, biologically relevant organic molecule essential for life on Earth. In addition to natural proteins, researchers can custom-create proteins with specific characteristics, structures, and properties. This includes designing proteins that can attach to different surfaces, including minerals like mica. Controlling and understanding protein attachment is essential for the assembly of advanced bio-inspired materials.
A team of researchers from the Pacific Northwest National Laboratory (PNNL), the University of Washington (UW) and Lawrence Berkeley National Laboratory (Berkeley Lab) worked together to track how specially designed protein nanorods moved across a mica surface. Their findings were recently published in the Proceedings of the National Academy of Sciences. The team created a series of protein nanorods of varying sizes specifically designed to bind to mica in partnership with the Institute for Protein Design at the University of Washington. The researchers then used high-speed microscopy to see the individual nanorods spinning in real time.
“We were able to track the protein nanorods at unprecedented levels of resolution,” said Shuai Zhang, assistant research professor in the Department of Materials Science and Engineering at UW, who has a joint appointment with the PNNL. “The atomic force microscope we used is incredibly powerful, allowing us to see the movements of each molecule in real time.”
To accurately observe protein rotation, the researchers had to study the protein-mica system in water. This environment mimics the conditions for protein assembly on real mineral surfaces.
Understand the different movements
Observation of the system under the microscope produced massive amounts of data. The sheer volume of data made analysis difficult. The Berkeley Lab team solved this problem by developing a new machine learning algorithm that dramatically reduced the time needed to process images. From there, the researchers were able to observe how fast the proteins moved and how much they rotated per individual motion.
Their observations showed that the proteins mostly behaved as expected, that is, they moved in small jumps, following a pattern of movement dating back to Einstein. However, the proteins sometimes made large and rapid jumps that the model could not explain.
To get to the bottom of these different types of movement, the team performed simulations based on the microscopy data. They found that protein-surface binding energy controls protein rotation. Most of the time, the proteins remain tightly bound to the surface of the mica, being able to perform only small movements. Sometimes they appear to briefly detach from the mica. During these short periods of time, proteins can move quickly in big jumps.
“Comparing our observational data and our simulations allowed us to identify the two types of protein movement,” said PNNL chemist Ben Legg. “We believe that large jumps have important consequences for the assembly of protein-mineral structures.”
Understanding how individual biological molecules move can help researchers develop better methods for assembling large numbers of proteins onto surfaces.
This work was funded by the Department of Energy through the Center for the Science of Synthesis Across Scales and Science Discovery through Advanced Computation (SciDAC) program. The PNNL research team also included James De Yoreo. The UW team included Harley Pyles and David Baker. The Berkeley Lab team consisted of Robbie Sadre, Talita Perciano, E. Wes Bethe and Oliver Rübel.
Reference: “Rotational dynamics and transition mechanisms of surface-adsorbed proteins” by Shuai Zhang, Robbie Sadre, Benjamin A. Legg, Harley Pyles, Talita Perciano, E. Wes Bethel, David Baker, Oliver Rübel and James J. De Yoreo, April 11, 2022, Proceedings of the National Academy of Sciences.