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Neu and Seelbinder wanted to answer two fundamental questions. How does a mechanical environment affect a cell?
They discovered that they have the potential to tackle major health obstacles and advance artificial tissue engineering.
Their research found that mechanical forces guide the development of a cell through the reorganization of its nucleus and could influence future diseases.
Neu said that they were interested in the development of healthy cells and the health of a cell.
Tension is one of those forces. The reorganization of the nucleus is caused by tension stretching the cell. The modification could change the expression of genes, which could indicate diseases in patients.
Neu and Seelbinder were able to conclude that scientists could influence a cell of their own. Researchers can change the environment by manipulating the tension in a cell, which could be used to create more authentic artificial tissues.
The discovery was made.
Seelbinder discovered that mechanical forces shape the nucleus while studying the cardiovascular cells of embryotic mice.
The nucleus is large, contains all of the genes, and has mechanical connections to all parts of the cell. There is a clear pattern that should be investigated more closely.
The perfect model to study nuclear deformation is heart cells, because they contract on their own. The cells are very sensitive to their environment.
The nucleus was stiff, rigid and dense in certain areas, Seelbinder noticed. The nucleus appeared to be disorganized in other areas.
Neu said that the nucleus takes on a certain structure and is not just a soft gel. There are defined forces that are happening because the heart cells are contracting. The mechanics are fascinating because the forces are being transferred to the cell substructures.
The result of mechanical forces and tension moving through cells was concluded by Neu and Seelbinder. Structural elements of the nucleus are reorganized by those contractions.
Neu said the discovery led to a major collaborative effort at the College of Engineering and Applied Science. The University of Colorado's Paul M. Rady Department of Mechanical Engineering, the Department of Molecular, Cellular and Developmental Biology, the University of Pennsylvania, and the University of Purdue University collaborated to confirm that the same patterns occur in humans.
Human health impacts.
Understanding how the nucleus is organized is a fundamental subject area. The location of genes in the nucleus is important for their expression.
Animals that experienced nuclear reorganization later in life developed pathology with symptoms that an older human with cardiovascular disease or hypertension might experience.
They observed the expression of the genes in the adult stage of the mice. The loss of cell identity and activity is caused by that. In the case of heart cells, contraction stopped.
The mechanics and the organization of the nucleus are important at later stages of life. Someone develops heart disease.
The researchers studied patients with heart conditions that make it harder for the heart to pump blood. Seelbinder explained that cardiomyopathy was a good condition for their work because it changed the heart's mechanical environment.
Cardiomyopathy causes fewer contractions and less nuclear deformation. The cellular identity is declining.
"If you use markers like how much blood does the heart pump and correlate it over the reorganization of the nucleus, it was highly predictive," Seelbinder said. "That means you can look at the organization of the nucleus and see if that organ functions well or not."
The findings became one of the most impressive things they discovered. It opened the door for more than just diagnostic potentials.
Artificial tissue.
Neu and Seelbinder's research could change the way artificial tissue engineering is done. There are gaps in understanding of the relationship between mechanical forces and cell development.
Neu said that if researchers know how the heart develops, they can mimic the process.
Their research shows how the path of development can be used to set the stage for new technologies.
Neu said that pharmaceutical companies may want to screen new drugs. It may be possible to screen candidate drugs that might be most effective in humans if you can create a miniature model of a person.
Nature Biomedical Engineering has more information on Nuclear deformation guides chromatin reorganization in cardiac development and disease. There is a DOI of 10.1038/s41551-021-00823-9.
The journal contains information about Biomedical Engineering.
Nuclear-deformation-advance-artificial-tissue.html was retrieved fromphys.org on December 2, 2021.
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