Study finds neurodegenerative disease progression linked to proteins in brain

Tau and tubulin proteins are primarily responsible for many neurodegenerative diseases, including Alzheimer’s and Parkinson’s. The buildup of these proteins in the brain is mostly to blame for the progression of neurodegenerative disorders.

Jiali Li, a physics professor at the University of Arkansas, and her colleagues created a novel silicon nitride nanopore-based sensing device in response to a doctoral student’s wish to examine tau and tubulin proteins. Acharjee et al. present the gadget in AIP Publishing’s Journal of Applied Physics, which is meant to offer volume information on tau and tubulin protein molecules and their aggregation states at the single-molecule level inside their native environment.

“Ohm’s Law is the basic physics that enables the nanopore device to sense protein molecules,” said Li. “A tiny hole — from 6 to 30 nanometers — is made in a thin silicon nitride membrane and supported by a silicon substrate. When that is placed into a solution with salt ions, applying an electric voltage drives the ions’ flow through the hole, or nanopore. This, in turn, generates an open pore ionic current.”

When a charged protein molecule — often thousands of times larger than the ions — is near the nanopore, it also gets driven into the nanopore and blocks the flow of some ions. This causes the open pore current to drop.

“The amount of current drop produced by a protein molecule is proportional to the protein’s volume or size and shape,” said Li. “This implies that if protein A binds to protein B, they will cause a current drop proportional to the volume of A+B, and an aggregated protein A will cause approximately multiple amounts of current drop.”

This allows Li and her group to look at the protein binding and aggregation within a nanopore device. The amount of time a protein stays in a nanopore is inversely proportional to its charge, which also provides useful information about a protein molecule.

“Our study shows that a silicon nitride nanopore device can measure volume information of tau and tubulin protein molecules and their aggregation under different biological conditions, and this gives us a better understanding of the protein aggregation process, as well as developing drugs or other therapeutic methods to treat neurodegenerative diseases,” said Li.

Using their solid-state nanopore device, along with other nanotechnology tools, “we plan to study the mechanism of protein aggregation under different biological conditions systematically, such as temperature, pH, and salt concentration,” she said.