Our bodies are alive with activity and full of proteins stuck in fatty membranes or floating in and out of watery cells. Scientists have now been able, for the first time, to capture a picture of the dance between the two: the fluid tango of proteins and lipids as they normally move in cells.
“We go beyond simply taking individual snapshots, which give structure but not dynamism, to continuously recording molecules in the water, and their original state.” He says Qian Chen, a materials scientist and engineer at the University of Illinois Urbana-Champaign (UIUC), who led the team and Describes their work Like “movie making.”
“We can really see how proteins change their conformation and, in this case, how the self-assembled protein-lipid structure fluctuates over time.”
By tweaking a widely used imaging technique called Transmission electron microscopeChen's team captured moving images of membrane protein “nanodiscs” in liquid. these Nanodiscs They consist of proteins embedded in a lipid bilayer similar to the cellular membranes in which they are normally found.
The team called their method “electronic video imaging,” and validated the video data by comparing it to atomic-level computer models of how molecules move based on the laws of physics.
It was thought that the movement of membrane-bound proteins was somewhat limited, due to how lipids hold them in place. However, the researchers saw that interactions between proteins and lipids occur over much greater distances than previously thought.
Membrane proteins are cell gatekeepers, sensors, and signaling receptors, so this technology could lead to huge advances in our understanding of how they work.
With current technologies, proteins are usually frozen or crystallized so that they do not move, distort the image, or be damaged by the X-rays or electron beams used to image them. This gives a lifeless picture of a fixed protein that normally folds and bends, leaving scientists to infer how it interacts with other molecules based on its structure.
Alternatively, some imaging techniques use a fluorescent molecular tag Track particles as they moveInstead of watching the protein directly.
In this case, the researchers placed a drop of water inside two thin graphene sheets to protect them from the vacuum of an electron microscope. Suspended in the water drop were nanodiscs of unlabeled proteins and lipids, which the team watched “dancing” together as they would in their natural aquatic environment.
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Materials scientists You might try For at least ten years to image the activity of biological molecules in fluids, but they were unable to clearly observe ongoing protein dynamics.
Through some subtle modifications to this approach, Chen and his colleagues imaged their protein and lipid assemblies in real time, for minutes, not microseconds. Importantly, they slowed the rate at which electrons penetrated the sample and worked on the graphene scaffold, successfully imaging the lipoprotein complex in action.
“Right now, this is the only experimental way to capture this kind of movement over time.” He says John Smith, a graduate student in materials engineering at UIUC, is the first author of this paper.
“Life is fluid, it is in motion. We are trying to get to the finer details of this connection in an experimental way.”
As for other efforts, improved imaging techniques are revealing astonishing details about all kinds of microscopic events — from observing how a virus's outer shell forms to spotting the proteins that break down into clumps in diseases like Alzheimer's.
Add artificial intelligence to the mix, predicting the 3D shape of almost every protein known to science, and it certainly seems that a new era of biological research has been opened up.
The research was published in Advancement of science.
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