Single-Molecule Imaging Reveals How Copper Protein Behaves in Living Cells

A University of Houston chemist is using an imaging technique that tracks individual copper transport proteins inside living cells to investigate how copper imbalances in the body may contribute to neurodegenerative diseases such as Alzheimer's, Parkinson's and ALS. The root cause of these incurable diseases remains largely unknown, and existing medications only manage symptoms, but researchers have long linked copper imbalances within neurons to severe neurological disorders. Tai-Yen Chen aims to pinpoint the exact cellular pathways that fail, providing foundational knowledge needed to develop future cures and guide therapeutic strategies.

Chen's work centers on CTR1, a protein that brings copper into cells. Recently published findings, which appeared in Nature Communications, challenged a long-standing view of how this key transport protein works, opening new questions about how copper regulation influences cell function and development.

"We discovered that a protein called CTR1, which brings copper into cells, is much more dynamic than scientists previously thought," Chen said. "We found that when copper levels become too high, CTR1 changes its structure in a way that helps reduce copper uptake. This appears to be an important mechanism that cells use to maintain healthy copper levels."

Chen's team is now investigating how this copper-regulating behavior connects to signaling in human neurons and how disruptions in this process may contribute to neurodegenerative disease. Using advanced imaging tools developed in Chen's lab, the team can watch and measure individual CTR1 protein complexes inside individual cells, allowing researchers to see differences from cell to cell and detect rare protein behaviors that may be hidden when only large groups of cells are measured at once.

Traditional biochemical methods are powerful for measuring overall trends, but they typically report an average signal from many cells and proteins, which can obscure small differences between individual cells, unusual protein behaviors, or short-lived events that may matter in disease. Chen's single-molecule approach offers a closer look at how individual proteins behave inside living cells, giving researchers a more detailed view of copper regulation. The approach could eventually help scientists study other diseases and biological processes shaped by rare molecular events or cell-to-cell differences.

"Some neurological diseases have been pretty much unsolvable in the past because there were no effective approaches to ask these complex questions," Chen said. "Now, with our unique imaging approach, new questions can be asked quantitatively, which can provide insight and move the field forward."