To find a criminal suspect, you need to be able to sketch their portrait or find a unique identifier. It’s the same for the proteins that are responsible for example for diseases such as Alzheimer’s and Parkinson’s. Researchers at the University of Fribourg’s Adolphe Merkle Institute (AMI) and the University of Michigan have demonstrated a technique for precisely measuring the properties of individual protein molecules in a liquid solution.

Scientists believe some neurodegenerative diseases such as Alzheimer’s and Parkinson’s are caused by misshapen proteins. Proteins are essential for every cell. The body manufactures them in a variety of complex shapes that can transmit messages between cells, carry oxygen, and perform other important functions. Sometimes, however, they don’t form properly. The misshapen proteins can clump together and develop into masses in the brain. The sticky tangles block normal cell function, leading to brain cell degeneration and disease.

Measuring proteins in blood and other body fluids could therefore unlock valuable information, as these molecules are a vital building block in the body. The researchers at AMI and the University of Michigan who developed the new identification approach say though that current techniques for identifying proteins are similar to identifying a person based only on their weight and height.

They believe that their method could help solve the problem by measuring an individual molecule’s shape, volume, electrical charge, rotation speed and propensity for binding to other molecules. The researchers call this information a «5-D fingerprint» and believe that it could uncover new information that may one day help doctors track the status of patients with neurodegenerative diseases and possibly even develop new treatments.

To take the detailed measurements, the research team uses a nanopore, a passage in a surface that is just ten to 30 nanometers wide – so small that only one protein molecule can fit through at a time. The nanopore is filled with a salt solution and an electric current is passed through the solution. As a protein molecule tumbles through the passage, its movement causes tiny, measurable fluctuations in the electric current. By carefully measuring this current, the researchers can determine the protein’s unique five-dimensional signature and identify it nearly instantaneously.

Michael Mayer, the lead author of a paper recently published by the journal Nature Nanotechnology and AMI’s chair of Biophysics, says identifying individual proteins could also help researchers gain a better understanding of exactly how amyloid proteins are involved with neurodegenerative disease.

«Amyloid molecules not only vary widely in size, but they tend to clump together into masses that are even more difficult to study,» said Mayer, who launched the research at the University of Michigan and finalized it in Fribourg. «Because it can analyze each particle one by one, this new method gives us a much better window into how amyloids behave inside the body.»

Ultimately, the team aims to develop a device that doctors and researchers could use to quickly measure proteins in a sample of blood or other body fluids. This goal is likely several years off; in the meantime, they are working to improve the technique’s accuracy, honing it in order to get a better approximation of each protein’s shape. They believe that in the future, the technology could also be useful for measuring proteins associated with heart disease and in a variety of other applications as well.

Article in Nature Nanotechnology
Yusko E.C., Bruhn B.R., Eggenberger O.M., Houghtaling J.,  Rollings R.C., Walsh N.C., Nandivada S., Pindrus M., Hall A.R., Sept D., Li J., Kalonia D.S., Mayer M. Real-time shape approximation and fingerprinting of single proteins using a nanopore, Nat. Nanotech., 2016