Scientists receive gout on the nucleus of the cell

"This noninvasive strategy for measuring the properties of materials in living cell cores can provide essential knowledge to understand the nucleus of the cell," explains Alexandra Zidovska, assistant professor of physics at the University. of New York and lead author of the research. the last issue of the journal Letters of physical examination (PRL). "We believe that further development of this approach may have potentially important implications for the diagnosis and treatment of the disease."

Other researchers in the study included Christina Caragine, a Ph.D. student at New York University, and Shannon Haley, an undergraduate student at the College of Arts and Sciences at the University of New York. at the time of work and currently a doctoral student at the University of California at Berkeley.

The material properties of the cell nucleus and its constituents are essential for all cellular processes as they affect the most fundamental biological processes, such as the reading of the genetic information of the DNA molecule, its transcription into RNA and its translation into proteins.

In particular, the viscosity of the nucleoplasm, or the thickness of the solution inside the nucleus of the cell, influences the speed and distance traveled by molecules and organelles within the nucleus. . Scientists believe that these material properties change in a number of human diseases. However, measuring them is a long-standing challenge – the previous methods were based on interventions that were thwarted by cell response.

In the PRL study, the researchers aimed to overcome this problem by using natural cell dynamics and events occurring inside the nucleus of the human cell to infer the physical properties of the nucleus and its constituents in living cells.

Specifically, they used confocal two-color high-resolution disk confocal microscopy, an imaging technique that records the spatial and temporal behavior of living cells. Using this technique, they monitored changes in the shape of the nucleoli, the larger structures within the nucleus, during their fusion, as well as very small surface fluctuations.

Remarkably, nucleolar fusion occurs many times in the life of a human cell, but there is no way to predict when and where this will happen in the nucleus of the cell, Zidovska points out. Thus, to identify a merger, she adds, you have to look at the right place at the right time.

Zidovska and his team have developed a new experimental procedure that captures these elusive fusion events.

This non-invasive approach avoids disrupting natural cellular activity while serving as a window to this dynamic. As a result, he detected aspects of the cell that were previously unknown.

In particular, the method has shown that human nucleoli behave like liquid droplets. In addition, this allowed scientists to measure the physical properties of the surrounding nucleoplasm – a breakthrough indicating that the nucleoplasm surrounding the nucleolar droplets had an extremely high viscosity; in fact, it is 100 times higher than that of honey, which slows the coalescence of nucleolar droplets in healthy cells.

"Since nucleoli actively transcribe DNA, slow coalescence could prevent disruption of nucleolar transcription, thus contributing to the health of a cell," Zidovska observes.

In contrast, she adds, human nucleoli are known to alter their shape and size in many diseases, such as cancer, Alzheimer's disease and Parkinson's disease, as well as in human aging . By understanding the forces that cause these changes, such as the possible differences in nucleolar droplet viscosity, scientists could better understand the nucleolus and nucleus of healthy and diseased cells.

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