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A collaborative study led by researchers from Rutgers University-New Brunswick has unveiled intriguing insights into the behavior of biomolecular condensates—small protein blobs found in human cells. This research indicates that these droplets can transition from a viscous, honey-like state to a solid, candy-like consistency.
The study revealed that biomolecular condensates solidify when they contain a high concentration of the protein alpha-synuclein. This protein is notorious for its aggregation in the brain cells of individuals suffering from Parkinson’s disease, a serious neurodegenerative condition.
The researchers noted that their work represents a pioneering effort to quantify the dynamics of these condensates within living cells, underscoring the significance of examining their mechanical properties, which play a critical role in various biological processes and health issues.
“Our ability to observe how these condensates evolve from liquid to solid states in live cells enhances our understanding of the development and progression of diseases like Parkinson’s,” stated Zheng Shi, a senior author of the study and assistant professor in the Department of Chemistry and Chemical Biology at Rutgers.
In the last decade and a half, advancements in technology have allowed scientists to delve deeper into the nature of biomolecular condensates, which are unique in that they do not possess a membrane boundary. Understanding these structures has proven vital for grasping cell biology and the underpinnings of disease.
The research team at Rutgers is particularly focused on these microscopic protein aggregates to uncover novel cellular mechanisms.
“Through our research, we’ve pinpointed the factors that initiate the transition from liquid to solid in these condensates,” explained Shi, who is also involved in the Cancer Pharmacology Program at the Rutgers Cancer Institute of New Jersey.
Parkinson’s disease leads to the degeneration of dopamine-producing neurons, which are essential for regulating movement. As the disease progresses, the loss of these neurons results in increasingly severe symptoms.
Alpha-synuclein’s role in Parkinson’s is significant; the protein misfolds and aggregates to form Lewy bodies, which are detrimental to neuron health.
To achieve their findings, the researchers developed innovative tools to surpass prior restrictions that limited measurement capabilities to in vitro studies.
“Our method allows for the first time direct and quantitative measurement of the material properties of condensates in live cells,” remarked Huan Wang, a doctoral student and principal author of the paper. “This represents a technological advancement that opens new avenues for investigating protein condensates.”
The breakthrough lay in creating miniature tools that could probe the condensates without damaging the hosting cells. Researchers designed tiny micropipettes capable of accurately measuring minute volumes of materials, leveraging the capillary effect—a phenomenon where liquid naturally rises or falls within a narrow space, such as a thin tube.
By carefully inserting micropipettes into the condensates, researchers could extract liquid or solid material without disrupting the cell’s integrity. Through monitoring the pressure and observing how the condensates deform and flow within the micropipette, critical properties such as viscosity and surface tension were measured.
The team’s aim is to further explore and quantify the properties of these condensates in living cells and their relationship to various diseases.
“This research paves the way for new investigations into the early stages of neurodegenerative diseases and potential treatment strategies,” added Shi.
Additional researchers from Rutgers involved in this study included Jean Baum, a Distinguished Professor; Mengying Deng, a postdoctoral associate; Jordan Elliott, a doctoral student; as well as Zhiping Pang, a professor; and Xiao Su, a guest researcher from the Child Health Institute of New Jersey at Rutgers Robert Wood Johnson Medical School. Conor McClenaghan, an assistant professor at the Center for Advanced Biotechnology and Medicine, also contributed to this research.
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