Scientists reveal how proteins associated with Parkinson’s disease convert biomolecular condensates

An international research collaboration led by New Brunswick scientists at Rutgers University who examined microscopic blobs of proteins found in human cells discovered that there is a morph from almost honey-like substances to hard candy-like solids.

Known as biomolecular condensates, these mystical droplets solidify when carrying a high percentage of the protein’s alpha-cynuclein, scientists report on scientific advances. Alpha-synuclein mass is common in brain cells in Parkinson’s disease patients.

Scientists said their findings mark the first successful efforts known to quantify the condensate dynamics of living cells, and highlight the importance of studying the mechanical properties of biomolecular condensates.

“Measurement of how these condensates change from liquid to solid in living systems allows us to better understand how diseases like Parkinson’s disease develop and advance,” said Zheng Shi, assistant professor in the Department of Chemistry and Biology at Rutgers School of Arts and Sciences and a senior author of the study.

Over the past 15 years, scientists have adopted advanced techniques to examine in detail biomolecular condensates that lack membrane boundaries. They specify them as important to understand cell biology and the origins of disease.

Rutgers scientists are zeroing into microscopic clumps of proteins in the hopes of exploring new cellular mechanisms.

“Our research has enabled us to identify factors that lead to the liquid-to-solid transition of these condensates,” says Sy, who is also a member of the Cancer Pharmacology Program at the Rutgers Cancer Institute, New Jersey.

In patients with Parkinson’s disease, they produce dopamine-producing brain cells (a brain chemical that is essential for motor control). The disease progresses over time, and symptoms worsen when more neurons are lost.

Alphasynuclein plays an important role in Parkinson’s disease as proteins are misfolded and aggregated, forming pathological forms called Lewy bodies that are toxic to neurons.

To make their discoveries, scientists have developed a set of tools that can overcome previous limitations that allow only test tube measurements.

Huan Wang, a doctoral student in the Faculty of Chemical Chemistry and the first author of the study, said: “It’s a technological leap that opens up new ways to study protein condensate.”

The key is to develop tools as small as the biomolecule condensation itself, allowing the globular shape to be examined without destroying the cells that carry these condensates.

The researchers created microscope pipettes called micropipettes, and accurately measured small amounts of liquid.

This technique utilized the capillary effect. This is a physical phenomenon in which liquids naturally rise or fall into small spaces such as thin glass tubes.

Scientists carefully inserted micropipettes into the condensate, penetrating them, pulling out the liquid or solid material inside. By controlling the pressure and observing how the condensate deforms and flows within the micropipette, scientists measured important properties such as viscosity (liquid thickness) and surface tension (how the liquid is retained).

The researchers said their goal was to measure and better understand the properties of condensate in living cells and their effects on disease.

“This opens up new tools for research into the early stages of neurodegenerative diseases and their treatment,” Shi said.

Dragomir Milovanovic’s group at the German Center for Neurodegenerative Diseases in Berlin also contributed to this study.