Researchers have developed a groundbreaking microscopy technique called ONE (One-step nanoscale Expansion) that allows visualization of individual protein structures using a standard light microscope. This revolutionary method could enable early detection of neurodegenerative diseases like Parkinson’s disease, which are caused by protein misfolding. ONE microscopy represents a significant advancement in the field of structural biology and has been hailed as one of the ‘seven technologies to watch in 2024’ by the journal Nature.
Revolutionizing Protein Imaging with Conventional Microscopes
The ability to visualize the three-dimensional structure of proteins is crucial for understanding their function and the role they play in diseases. However, until now, achieving this level of detail has required the use of expensive and specialized techniques like electron microscopy and cryo-electron microscopy.
Researchers at the University Medical Center Göttingen (UMG) in Germany have developed a groundbreaking method called ONE microscopy that overcomes these limitations. By using a simple but effective trick, they have found a way to visualize individual protein molecules with a conventional light microscope, achieving a resolution of around one nanometer – about 100,000 times smaller than the diameter of a human hair.
Expansion Microscopy: Unlocking the Nanoscale World
The key to ONE microscopy is the use of a water-absorbing gel that acts as a scaffold for the cells and their internal structures. When this gel absorbs water, it expands up to 15 times its original size, causing the molecules within the sample to move apart evenly and become larger. This expansion allows the researchers to image individual protein fragments using a standard light microscope, circumventing the diffraction limit that typically limits the resolution of these instruments.
Combining this expansion technique with artificial intelligence-based image analysis, the researchers were able to reconstruct the three-dimensional structure of individual protein molecules from two-dimensional fluorescence images. This breakthrough represents a significant advancement in the field of structural biology, as it makes it possible to visualize the entire structure of complex proteins, including flexible components that are difficult to capture using other methods.
Towards Early Detection of Neurodegenerative Diseases
One of the most exciting applications of ONE microscopy is its potential to aid in the early detection of neurodegenerative diseases like Parkinson’s disease. These diseases are often characterized by the misfolding and aggregation of specific proteins, such as alpha-synuclein in the case of Parkinson’s.
Using ONE microscopy, the researchers were able to image and classify the aggregates of alpha-synuclein in cerebrospinal fluid samples from Parkinson’s patients. This opens up the possibility of a visual diagnosis of protein misfolding diseases based on easily accessible samples, such as blood or cerebrospinal fluid. Early detection is key for effective treatment, as it allows for intervention before the brain is too severely damaged. With ONE microscopy, clinicians may have a new tool to identify these diseases at an early stage, leading to improved patient outcomes and personalized treatment options.
