The first studies of a single protein paved the way for increasing understanding of the disease


May 03, 2023

(Nanowerk NewsThe Nottingham Trent University team said the research – the first of its kind – allowed them to see how proteins behave in their natural environment and could help better understand disease-related proteins and how they respond to certain therapies.

The research has been published in Nano Letters (“Optical Monitoring of In Situ Iron Loading into a Single Native Ferritin Protein”).

The research involved using very high concentrations of light, when the light is transmitted through specially engineered nanostructures, generating just the right amount of force to capture and hold a single protein in a liquid without damaging it.

The technology is able to detect how light is scattered and researchers can analyze this unique data to reveal how proteins behave in real-time.

Protein is studied in its natural fluid environment, because the team’s technique can mimic the body by changing factors such as salt concentration, pH or oxygen levels.

As a proof of concept the researchers studied ferritin, a blood protein that stores and releases iron to prevent diseases associated with iron dysregulation, such as anemia.

During the study, they were able to tell the difference between ferritin with and without iron – as the data revealed differences in their weight and movement – ​​and even the point at which ferritin without iron begins to capture and store iron.

They say the research has deepened the understanding of the iron absorption mechanism of the protein ferritin, which could lead to new therapies for iron-related diseases.

To date, studies of ferritin have only been able to use ensemble measurements to characterize a large number of proteins, which provides limited information about their structural changes.

The researchers argue that because protein changes occur before disease symptoms, their work may make it possible to identify and treat various diseases much earlier.

“To be able to see things beyond your vision, you first need the right technology. Our nanostructure allows us to observe proteins at the nanoscale,” said lead researcher Dr Cuifeng Ying from Nottingham Trent University’s School of Science and Technology.

He said: “This technique allows us to study the behavior of a living protein by using high-intensity light to trap, retain and study it in its own environment. Usually you need to study many proteins together to see how the groups respond.

“Many proteins are associated with disease; if we can get to the root of the problem then we can potentially address it better and earlier.”

Arman Yousefi, PhD candidate at Nottingham Trent University, and first author of the study, said: “Scattered light gives us a unique fingerprint to show us how proteins behave. With respect to ferritin, we observed a rigid and relaxed state of the protein with and without iron and even the process of collecting and storing iron from its environment.”

Mohsen Rahmani, Professor of Engineering at NTU and Royal Society Wolfson Fellow, added: “This technology and technique gives us the potential to identify protein changes in relation to disease onset and development. We can look at a lot of proteins and see how they react to different drugs. In the future, this breakthrough could play a key role in increasing survival rates and reducing healthcare costs.

“There were no tools before that would allow us to study proteins in this way without damaging them.


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