CHICAGO, Sept. 29 (Xinhua) -- The type and direction of the force on a cell alters gene expression by stretching different regions of DNA, researchers at University of Illinois (UI) and collaborators in China found in a study.

The researchers developed a method that allows them to move a magnetic bead in any direction, giving them a picture of the ways forces act on a cell in 3D. They call it three-dimensional magnetic twisting cytometry, according to a news release posted on UI's website on Tuesday.

They found that the force from the magnetic bead caused a rapid increase in expression for certain genes, but the amount of the increase depended on the direction the bead moved. When the bead rolled along the long axis of the cell, the increase was the lowest, but when the force was applied perpendicularly across the short axis of the cell, gene activity increased the most. When the bead was moved at a 45-degree angle or rotated in the same plane as the cell to induce shear stress, the response was intermediate.

"These observations show that gene upregulation and activation are very sensitive to the mode of the applied force, when the magnitude of the force remains unchanged," said study leader Ning Wang, a professor of mechanical science and engineering at UI.

In further experiments, the researchers found that the reason for the difference lies in the method that the forces are relayed to the cell's nucleus, where DNA is housed. Cells have a network of support structures called the cytoskeleton, and the main force-bearing elements are long fibers of the protein actin. When they bend due to a force, they relay that force to the nucleus and stretch the chromosomes.

These actin fibers run lengthwise along the cell. So when the force strains them widthwise, they deform more, stretching the chromosomes more and causing greater gene activity, the researchers found.

"A stress fiber is like a tense violin string. When a stress is applied across the short axis of the cell, it's just like when a person plucks a violin string vertically from the string's direction to produce a louder, more forceful sound," Wang said.

In the next step, the researchers will create disease models to see how different forces might help explain the mechanism of certain diseases, and to identify possible therapeutic targets or applications.

"In certain diseases, such as aortic valve calcification, arterial atherosclerosis, liver fibrosis or malignant tumors, these cellular responses and adaptation go awry, causing the tissues and organs to function abnormally," Wang said. "This is the first time that the mechanism of living cells' different biological responses to the direction of forces at the level of genes has been revealed, so perhaps with our three-dimensional approach we can understand these diseases better."

The study, supported by the U.S. National Institutes of Health and the National Science Foundation of China, has been published in the journal Nature Communications. Enditem

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