Proteins are essential to the function of every cell. Measuring
their properties in blood and other body fluids could unlock valuable
information, as the molecules are a vital building block in the body.
The body manufactures them in a variety of complex shapes that can
transmit messages between cells, carry oxygen and perform other
Sometimes, however, proteins don't form properly. Scientists believe
that some types of these misshapen proteins, called amyloids, can clump
together into masses in the brain. The sticky tangles block normal cell
function, leading to brain cell degeneration and disease.
‘In research that could lead to advances against neurodegenerative diseases, researchers have demonstrated a technique for measuring the properties of individual protein molecules floating in a liquid.
But the processes of how amyloids form and clump together are not
well understood. This is due in part to the fact that there's currently
not a good way to study them. Researchers say current methods are
expensive, time-consuming and difficult to interpret, and can only
provide a broad picture of the overall level of amyloids in a patient's
In research that could one day lead to advances against
neurodegenerative diseases like Alzheimer's and Parkinson's, University
of Michigan engineering researchers have demonstrated a technique for
precisely measuring the properties of individual protein molecules
floating in a liquid.The researchers
who developed the new technique believe that it could help solve the
problem by measuring an individual molecule's shape, volume, electrical
charge, rotation speed and propensity for binding to other molecules.
They 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. Their work is detailed in a paper published in Nature Nanotechnology
"Imagine the challenge of identifying a specific person based only
on their height and weight," said David Sept, a U-M biomedical
engineering professor who worked on the project. "That's essentially the
challenge we face with current techniques. Imagine how much easier it
would be with additional descriptors like gender, hair color and
clothing. That's the kind of new information 5-D fingerprinting
provides, making it much easier to identify specific proteins."
Michael Mayer, the lead author on the study and a former U-M
researcher who's now a biophysics professor at Switzerland's Adolphe
Merkle Institute, says identifying individual proteins could help
doctors keep better tabs on the status of a patient's disease, and it
could also help researchers gain a better understanding of exactly how
amyloid proteins are involved with neurodegenerative disease.
To take the detailed measurements, the research team uses a nanopore
10-30 nanometers wide - so small that only one protein molecule can fit
through at a time. The researchers filled the nanopore with a salt
solution and passed an electric current through the solution.
As a protein molecule tumbles through the nanopore, 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
"Amyloid molecules not only vary widely in size, but they tend to
clump together into masses that are even more difficult to study," Mayer
said. "Because it can analyze each particle one by one, this new method
gives us a much better window to 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 fluid. 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.
"I think the possibilities are pretty vast," Sept said. "Antibodies,
larger hormones, perhaps pathogens could all be detected. Synthetic
nanoparticles could also be easily characterized to see how uniform they