Protein clumps are associated with a variety of challenging diseases, such as ALS, Alzheimer's, and Parkinson's. Understanding the interactions of these proteins is complex. However, researchers at Chalmers University of Technology in Sweden have discovered a new way to trap many proteins in nanometer-sized traps. With this new approach, the behavior of proteins can be studied in unprecedented depth.

The image shows the protein trap, which consists of nanoscale chambers and polymers forming gates above. These "doors" open by raising the temperature by about 10 degrees. The polymer then changes shape into a more compact state, allowing proteins to move in and out. Source: Chalmers University of Technology | Julia Jerleback

Andreas Dahlin, professor at Chalmers University who led the research project, said: "We believe that our approach has huge potential to improve understanding of the early and dangerous processes of many different diseases and ultimately help people understand how to combat these diseases with drugs."

Proteins that form clumps in the body can cause a variety of diseases, including ALS, Alzheimer's and Parkinson's disease. If we better understand how clots form, we can find effective ways to dissolve them early on or even prevent them from forming entirely.

Andreas Dahlin, Professor at the Department of Chemistry and Chemical Engineering at Chalmers University of Technology. Image source: Chalmers University of Technology | Mikael Terfors

Today, there are various techniques to study the later stages of the process, when the clumps grow larger and form long chains, but until now, it has been difficult to track early developments because they were still very small at that time. Now, these new traps can help solve that problem.

Can be carried out for a long timehigh concentrationResearch

The researchers describe their work as the world's smallest floodgate, which can be opened and closed at the push of a button. These gates become traps, locking proteins into nanoscale chambers. The protein cannot escape, extending the time it takes to observe a protein at this level from one millisecond to at least an hour. The new method can also seal hundreds of proteins in a small volume, which is important for further understanding.

"The clumps we want to see and better understand are made up of hundreds of proteins, so if we are to study them we must be able to capture such large numbers of proteins," says Andreas Dahlin. "The high concentration in a small volume means that the proteins will naturally collide with each other, which is a big advantage of our new method."

Continued development of this method is needed in order to use this technique to study the course of specific diseases.

"The trap needs to be tuned to attract proteins that are relevant to the specific disease you are interested in," says Andreas Dahlin. "Our job now is to plan which proteins are best to study."

How the new trap works

The trap developed by the researchers consists of so-called polymer brushes located at the mouth of a nanoscale chamber. The proteins to be studied are contained in a liquid solution and are attracted to the chamber walls after being treated with special chemicals.

When the gate closes, the proteins break away from the cavity walls and begin moving toward each other. In a trap, you can study individual protein clumps, which can provide more information than studying many protein clumps simultaneously. For example, clumps may be formed by different mechanisms and have different sizes and structures.

These differences can only be observed on a case-by-case basis. In fact, proteins can be retained in the trap for almost any length of time, but currently, time is limited by the retention time of the chemical label. In this study, the researchers managed to maintain visibility for an hour.