Nanopore-based sensing device can provide volume information for tau and tubulin

Tau and tubulin proteins are one of the main causes of many neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease. Most of the progression of neurodegenerative diseases is linked to the aggregation of these proteins in the brain.

Inspired by one of her doctoral students who wanted to explore tau and tubulin proteins, Jiali Li, professor of physics at the University of Arkansas, and her group created a special detection device based on silicon nitride nanopores .

In Journal of Applied Physics, by AIP Publishing, Acharjee et al. present the device, which is designed to provide volume information about tau and tubulin protein molecules and their aggregation states at the single molecule level in their native environment.

To create the sensor, the team explored how proteins alter the current and voltage flowing through a nanopore system.

Ohm’s law is the basic physics that allows the nanopore device to detect protein molecules. A small hole -; from 6 to 30 nanometers -; is made in a thin membrane of silicon nitride and supported by a silicon substrate. When placed in a solution with salt ions, the application of an electrical voltage causes the ions to flow through the hole, or nanopore. This, in turn, generates an open-pore ion current.”

Jiali Li, Professor of Physics, University of Arkansas

When a charged protein molecule -; often thousands of times larger than – ions; is close to the nanopore, it is also drawn 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 volume or size and shape of the protein,” Li said. “This implies that if protein A binds to protein B, it will cause a current drop proportional to the volume of A + B, and an aggregate protein A will cause approximately several amounts of current drop.”

This allows Li and his group to examine protein binding and aggregation in a nanopore device. The residence time of a protein 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 the volume information of tau and tubulin protein molecules and their aggregation under different biological conditions, which gives us a better understanding of the protein aggregation process, as well as the development of drugs or other therapeutic methods to treat neurodegenerative diseases,” Li said.

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