Proteins that clump together play a significant role in various diseases, including ALS, Alzheimer’s, and Parkinson’s. Exploring the mechanisms of protein interactions has proven challenging, but researchers at Chalmers University of Technology in Sweden have made a groundbreaking discovery. They have developed a novel technique that allows for the capture of numerous proteins in nano-sized traps. These traps enable the study of proteins in a way that was not previously possible.
“We believe that our method has great potential to increase the understanding of early and dangerous processes in a number of different diseases and eventually lead to knowledge about how drugs can counteract them,” says Professor Andreas Dahlin, leader of the research project at Chalmers University.
The research findings have been published in the scientific journal Nature Communications, under the title “Stable trapping of multiple proteins at physiological conditions using nanoscale chambers with macromolecular gates.”
Understanding how protein clumps form is vital in developing effective methods to dissolve them or prevent them from occurring altogether. While numerous techniques exist to study the later stages of clump formation, it has been difficult to observe the early development when the clumps are still small. The newly developed traps address this challenge.
The researchers describe their creation as the world’s smallest gates, capable of being opened and closed with precision. These gates serve as traps, confining the proteins within nano-sized chambers. As a result, the proteins are prevented from escaping, allowing for prolonged observation time—up to at least one hour—as opposed to the previous limit of one millisecond. Additionally, multiple proteins can be enclosed within a small volume, facilitating comprehensive analysis.
“The clumps that we want to see and understand better consist of hundreds of proteins, so if we are to study them, we need to be able to trap such large quantities. The high concentration in the small volume means that the proteins naturally bump into each other, which is a major advantage of our new method,” explains Professor Dahlin.
Further development of the technique is necessary to study specific diseases accurately. The traps must be tailored to attract proteins associated with the particular disease under investigation. The team is currently identifying the most suitable proteins for further study.
Operating principles of the traps involve the use of polymer brushes located at the entrances of the nanoscale chambers. After undergoing a chemical treatment, the proteins are attracted to the chamber walls. When the gates are closed, the proteins are released from the walls and can begin to interact with each other.
The traps enable the examination of individual clumps of proteins, providing more detailed information compared to studying multiple clumps simultaneously. Different clumps can form through diverse mechanisms and exhibit varying sizes and structures. Analyzing them individually allows for the detection of these differences.
Currently, the retention time of proteins in the traps is limited by how long the applied chemical marker, which enables their visibility, persists. However, during the study, the researchers succeeded in maintaining visibility for up to an hour.
This breakthrough method opens up exciting possibilities for advancing our understanding of disease processes and developing targeted interventions to combat protein clumping. With further refinements, this technique may pave the way for innovative treatments for a range of challenging diseases.
1. What diseases are caused by protein clumps?
Protein clumps contribute to several diseases, including ALS, Alzheimer’s, and Parkinson’s. These clumps impair normal cellular functions and are challenging to treat.
2. How do the nano-sized traps work?
The traps utilize polymer brushes positioned at the entrances of the nanoscale chambers. These brushes attract proteins to the chamber walls after a chemical treatment. When the traps close, the proteins are released from the walls and can interact with each other.
3. What benefits do the traps offer for studying protein clumps?
The traps allow for the study of individual clumps of proteins, providing detailed information on different clump mechanisms, sizes, and structures. The ability to trap numerous proteins in a small volume enhances research capabilities.