Microtraps hold the key to understanding rare diseases

Newswise – Proteins that form clumps are found in many hard-to-treat diseases such as ALS, Alzheimer's and Parkinson's. The mechanisms by which proteins interact with each other are difficult to study, but now researchers at Chalmers University of Technology have discovered a new way to trap multiple proteins in nano-sized traps. Proteins inside the traps can be studied in a way that was not possible before.

“We believe that our method has great potential to increase the understanding of early and dangerous processes in various diseases and ultimately lead to knowledge about how drugs can counteract them,” says Andreas Dahlin, a professor at Chalmers who led the research project. .

Proteins that build up in our bodies cause a number of diseases, including ALS, Alzheimer's and Parkinson's. A better understanding of how clusters form may lead to effective ways to break them up at an early stage, or even prevent them from forming altogether. Nowadays, there are various techniques for studying the later stages of the process, when the clumps have become large and long chains have formed, but until now it has been difficult to follow the early development when they are still very small. These new traps can now help solve this problem.

Can study high concentration for a longer time

The researchers describe their work as the world's smallest gate that can be opened and closed at the push of a button. The gates become traps that lock proteins into chambers at the nanoscale. Proteins cannot escape, extending their observation time at this level from a millisecond to at least an hour. The new method also makes it possible to insert several hundred proteins in a small volume, an important feature for further understanding.

“The mags we want to see and understand better are made up of hundreds of proteins, so if we want to study them, we need to be able to capture such a large number. The high concentration of small volumes means that the proteins naturally collide. each other, which is the main advantage of our new method”, says Andreas Dalin.

In order for the technique to be used to study the course of specific diseases, continuous development of the method is required.

“The traps have to be adapted to attract proteins that are associated with the particular disease you're interested in.” What we are working on now is to plan which proteins are the most suitable to study,” says Andreas Dahlin.

How the new traps work

The gates, which the researchers created, consist of so-called polymer brushes, which are placed at the mouth of nano-sized chambers. The proteins to be studied are contained in a liquid solution and are attracted to the walls of the chambers after special chemical treatment. When the gate is closed, the proteins can be released from the walls and start moving towards each other. In traps, you can study individual clusters of proteins, which provides much more information than studying many clusters at once. For example, clusters can be formed by different mechanisms, have different sizes and different structures. Such differences can be noticed only if you analyze them one by one. In practice, the proteins can be kept in the trap for almost any length of time, but currently the time is limited by how long the chemical marker – which must be given to them – remains visible. During the study, the researchers managed to maintain visibility for an hour.

The research is presented in a scientific article “Stable capture of multiple proteins under physiological conditions using nanoscale chambers with macromolecular gates” It was recently published Communications of nature.

The article was written by Eustace Svirelis, Zeynep Adal, Gustav Emilsson, Jesper Medin, John Anderson, Radhika Vatikunta, Mats Hulander, Julia Jarlebark, Krzysztof Kolman, Oliver Olsson, Yusuke Sakiyama, Roderick IH Andrelin. Researchers are active at Chalmers University of Technology and the University of Basel.

Illustration: Chalmers University of Technology | Julia Jarlebark

Image caption: The image shows protein traps consisting of nanoscale chambers and polymers that form gates above. These “doors” are opened by increasing the temperature by about 10 degrees, which happens electronically. The polymers then change shape into a more compact state to allow the proteins to move in and out.