Scientists at the University of Chicago's Institute for Molecular Engineering are putting liquid crystals to work as detectors for the protein fibers implicated in the development of neurodegenerative diseases such as Alzheimer's. Their approach may lead to easier, less costly way to detect these fibers and to do so at a much earlier stage of their formation than has been possible before, the stage when they are thought to be the most toxic.
“It is extremely important that one develop techniques that allow us to detect the formation of these so-called amyloid fibrils when they're first starting to grow,” said Juan de Pablo, Ph.D., whose group did the new work. “We have developed a system that allows us to detect them in a simple and inexpensive manner. And the sensitivity appears to be extremely high.”
Amyloid fibrils are protein aggregates that are associated with the development of neurodegenerative diseases including Huntington's disease, Parkinson's, Alzheimer's, and mad cow disease, as well in type II diabetes, where they damage the pancreatic islets. Researchers would like to be able to study their formation both for therapeutic reasons and so that they can test the effect of new drugs on inhibiting their growth.
But the fibrils that are believed to be most harmful are too tiny to be seen using an optical microscope. So scientists have relied on elaborate and expensive fluorescence- or neutron scattering-based techniques to study them.
The de Pablo group took a completely different approach. They exploited the way a liquid crystal responds to a disturbance on its surface. The scientists made a film of a liquid crystal molecule called 5CB, which Dr. de Pablo called the “fruit fly” of liquid crystal research because it is so well studied. Then they applied chemicals to the 5CB film that caused the molecules to align in such a way as to block the passage of light.
Floating on top of the film was a membrane made of molecules resembling those found in the membranes of biological cells. And on top of that was water, into which the scientists injected the molecules that spontaneously form the toxic aggregates.
“As aggregates grow on the membrane, they imprint their shape into the liquid crystal underneath,” continued Dr. de Pablo, the Liew Family Professor in molecular engineering. “The liquid crystal molecules that are at the interface become distorted: they adopt a different orientation, so that light can now go through.”
This disturbance on the membrane, i.e., the imprint of the protein fibers, is transmitted down through the liquid crystal film, in effect amplifying it. The fibers might be tens of nanometers in diameter and a hundred nanometers long, far smaller than a red blood cell. But the disturbance they create is magnified by the liquid crystal so that it is large enough to be seen in polarized light with a simple optical microscope.
Seen through the microscope, the aggregates appear as tiny bright spots in a sea of black: bright where the liquid crystal has been disturbed to let light pass. “The liquid crystal is actually reporting what's happening to the aggregates at the interface,” according to Dr. de Pablo. “And these bright spots become bigger and adopt the shape of the actual fibers that the protein is forming. Except you're not seeing the fibers, you're seeing the liquid crystal's response to the fibers.”
The de Pablo team’s study (“Liquid Crystal Enabled Early Stage Detection of Beta Amyloid Formation on Lipid Monolayers”) appears in Advanced Functional Materials.