For the first time, scientists capture the protein-lipid dance on video: ScienceAlert

Our bodies thrive on activity and are packed with proteins that are trapped in fatty membranes or floating in and out of watery cells. Scientists have now captured the dance between the two for the first time: a liquid tango with proteins and fats as they normally move in cells.

“We go beyond taking individual snapshots, which provide structure but not dynamics, by continuously capturing the molecules in water, their initial state,” says Qian Chen, a materials scientist and engineer at the University of Illinois Urbana-Champaign (UIUC). ), who led the team and describes their work as ‘filmmaking’.

“We can really see how proteins change their configuration and, in this case, how the entire self-assembled structure of proteins and lipids fluctuates over time.”

By adapting a commonly used imaging technique called transmission electron microscopy, Chen’s team captured the vivid choreography of “nanodiscs” of membrane proteins in liquid. These nanodisks consist of proteins embedded in a lipid bilayer similar to the cell membranes in which they are commonly found.

The team has called their method “electron videography” and validated the video data by comparing it to atomic-level computer models of how molecules should move based on the laws of physics.

The movement of membrane-bound proteins was thought to be quite limited, given the way lipids hold them in place. However, the researchers saw that interactions between proteins and lipids occurred over much greater distances than previously thought possible.

Membrane proteins are the cell’s gatekeepers, sensors and signal receivers, so the technique could lead to huge advances in our understanding of how they work.

Existing techniques usually freeze or crystallize proteins quickly so that they do not move and blur an image, or become damaged by the X-rays or electron beams used to image them. This provides a lifeless image of a static protein that normally folds and bends, allowing scientists to infer how it interacts with other molecules based on its structure.

Alternatively, some imaging techniques use a fluorescent molecular label to track molecules as they move, rather than looking directly at the protein.

In this case, the researchers placed a drop of water in two thin layers of graphene to protect it from the vacuum of the electron microscope. Inside the water droplet were nanodiscs of unlabeled proteins and lipids, which the team observed ‘dancing’ together, just as they would in their natural aqueous environment.

frameborder=0″ allow=accelerometer; autoplay; clipboard writing; encrypted media; gyroscope; photo within photo; web-share” referrerpolicy=”strict-origin-when-cross-origin” allowfullscreen>

Materials scientists have been trying to film the activity of biological molecules in liquids for at least a decade, but they have been unable to clearly observe continuous protein dynamics.

With some careful tweaks to the approach, Chen and colleagues were able to image their protein-lipid assemblies in real time and for minutes, not microseconds. Importantly, they slowed the rate at which electrons entered the sample and worked on the graphene scaffold to successfully film the protein-lipid complex in action.

“Currently, this is really the only experimental way to film this kind of movement over time,” said UIUC materials science graduate student John Smith, first author of the paper.

“Life is fluid and it is in motion. We are trying to discover the finest details of that connection in an experimental way.”

As for other efforts, improved imaging techniques are revealing incredible detail about a variety of microscopic events — from watching a virus’s outer layer take shape to capturing the moment proteins break apart into clumps in diseases like Alzheimer’s.

Add in artificial intelligence to predict the 3D shape of almost every protein known to science, and it certainly seems like a new era of biological research has begun.

The research was published in Scientific progress.