Scientists at Nottingham Trent University and the Adolphe Merkle Institute have developed new technology which has made it possible to isolate and study how a single protein - 10,000 times thinner than a human hair - behaves and changes over time. The researchers say the work – the first of its kind – enables them to see how a protein behaves in its natural environment and that it could help better understand proteins linked to disease and how they might respond to certain therapies.
The research involves using a very high concentration of light which, when the beam is transmitted through a specifically engineered nano structure, generates the right amount of force to grasp and hold a single protein within the fluid without damaging it. The non-destructive technology is able to detect how the light is scattered and the researchers can analyse this unique data to reveal how the protein is behaving in real-time. The protein is studied in its natural liquid environment, as the team’s technique can mimic the body by altering factors such as salt concentration, pH, or oxygen levels.
As a proof of concept the researchers studied ferritin, a protein in the blood which stores and releases iron to prevent diseases associated with iron dysregulation, such as anaemia. During the study they were able to distinguish between the ferritin with iron and without – as the data revealed differences in their weight and movement – and even the point at which the ferritin without iron began capturing and storing iron. They say that the study has deepened understanding of the iron uptake mechanism of ferritin proteins, which could lead to new therapeutics for iron-related diseases. Until now, studies of ferritin have only been able to use ensemble measurements to quantify the characteristics of a large number of proteins, which provides limited information about their structural changes. The researchers argue that because protein changes occur before symptoms in illness, their work could make it possible to identify and treat a range of diseases much earlier.
"To be able to see things beyond your eyesight, you first need the right technology. Our nanostructure enables us to observe proteins at the nano-scale," says lead researcher Dr. Cuifeng Ying from Nottingham Trent University's School of Science and Technology and AMI BioPhysics alum. "This technique allows us to study the behaviour of a single living protein by using a high intensity light beam to trap, hold and study it in its own environment. Normally you would need to study many proteins together to see how the group responds," she adds. "Lots of proteins are linked to disease; if we can see the root problem then we can potentially treat them better and earlier."
According to the researchers, the scattered light provides a unique fingerprint to show how the protein is behaving. With regards to ferritin, they were able to observe the rigid and relaxed state of the protein with and without iron, and even the process of collecting and storing the iron from its environment. They believe this technology and technique could help identify protein changes in relation to disease emergence and progression, for example by observing how proteins react to different drugs.
Reference: Yousefi, A.; Ying, C.; Parmenter, C. D. J.; Assadipapari, M.; Sanderson, G.; Zheng, Z.; Xu, L.; Zargarbashi, S.; Hickman, G. J.; Cousins, R. B.; Mellor, C. J.; Mayer, M.; Rahmani, M. Optical Monitoring of In Situ Iron Loading into Single, Native Ferritin Proteins. Nano Lett. 2023, 23 (8), 3251–3258. https://doi.org/10.1021/acs.nanolett.3c00042.
Original text: Nottingham Trent University