Metallic probe detects fibrils from misfolded proteins in living cells

Rice University scientists have discovered a new way to look inside living cells and see the insoluble fibrillar deposits associated with Parkinson's disease.

The combined capabilities of two Rice laboratories – one that studies the misfolded proteins that cause neurodegenerative diseases and another that specialises in photoluminescent probes – led to the spectroscopic technique that could become a valuable tool for scientists and pharmaceutical companies.

The research by the Rice labs of Angel Martí and Laura Segatori appeared online this month in the Journal of the American Chemical Society.

The researchers designed a molecular probe based on the metallic element ruthenium. Testing inside live neuroglioma cells, they found the probe binds with the misfolded alpha-synuclein proteins that clump together and form fibrils and disrupt the cell's functions. The ruthenium complex lit up when triggered by a laser – but only when attached to the fibril, which allowed aggregation to be tracked using photoluminescence spectroscopy.

Researchers trying to understand molecular mechanisms of protein misfolding have had limited alternatives to monitor protein aggregation in cells, Martí said. A probe that can monitor the formation of aggregates should be of great value in the search for drugs that break up fibrils or prevent them from ever forming.

Two years ago, Martí, an assistant professor of chemistry and bioengineering, and Rice graduate student Nathan Cook revealed their metallic compounds that switch on like a light bulb when they attach to misfolded proteins; that study involved the beta amyloids that form plaques in the brains of Alzheimer's sufferers.