Tau and tubulin proteins are one of the main causes of many neurodegenerative diseases, including Alzheimer’s and Parkinson’s. Most neurodegenerative diseases are associated with the accumulation of these proteins in the brain.
Inspired by one of his doctoral students who wanted to study tau and tubulin proteins, Jiali Li, a professor of physics at the University of Arkansas, and his group created a special device based on silicon nitride nanopores.
in Journal of Applied Physics, AIP Publishing, Acharjee et al. A device designed to provide quantitative information on tau and tubulin protein molecules and their aggregation states at the single-molecule level in their native environment is presented.
To build the sensor, the team studied how proteins change the current and voltage flowing through the nanopore system.
Ohm’s law is the fundamental physics that enables nanowell devices to sense protein molecules. Small hole -; from 6 to 30 nanometers -; made of a thin silicon nitride membrane and supported by a silicon substrate. When this is done in a solution of salt ions, applying an electrical voltage causes the ions to flow through the holes or nanoholes. This in turn creates pore ionic currents.”
Jiali Li, professor of physics at the University of Arkansas
When a charged protein molecule -; usually thousands of times larger than ions -; Because it is located near the nanopore, it penetrates the nanopore and blocks the flow of some ions. This causes the open hole current to decrease.
“The amount of current drop from a protein molecule is proportional to the size or size and shape of the protein,” Lee said. “This means that if protein A binds to protein B, they will cause a current dip proportional to the volume of A+B, and the aggregated protein A will cause a current dip that’s about as many.”
This allows Lee and his group to see protein binding and aggregation inside the nanopore device. The residence time of a protein in a nanopore is inversely proportional to its charge, which provides useful information about the protein molecule.
“In our research, the silicon nitride nanopore device can measure the volume information of tau and tubulin protein molecules in various biological conditions and measure their aggregation, which leads to a better understanding of the protein aggregation process, as well as the development of drugs and other therapeutic methods to treat neurological disorders. ” Lee said.
With their solid-state nanowell device and other nanotechnology tools, “we plan to systematically study the mechanism of protein aggregation under different biological conditions, such as temperature, pH, and salt concentration,” he said.
Source:
American Institute of Physics
Journal reference:
Acharji, MC, etc. (2023) Characterization of Tau and Tubulin Protein Aggregation by Solid-State Nanopore Techniques and Atomic Force Microscopy. Journal of Applied Physics. doi.org/10.1063/5.0123688.
