Researchers at the Massachusetts Institute of Technology (MIT) have discovered that cells undergo a “cleanup” process to expel apparently unnecessary molecules before they begin to divide. Researchers believe that this wash helps the parent cells give their progeny a “new start” without all the junk that they have accumulated in their lives. In the long run, researchers say the findings may help fight neurodegenerative diseases and cancer.

Using a new method developed to measure the dry mass of cells, researchers have found that cells lose about 4 percent of their mass at the onset of cell division.

“Our hypothesis is that we are throwing away what the cells have accumulated, toxic elements, or what you don’t want there and aren’t functioning properly. That’s what newborn cells are more functional. It will make it possible to be born, “said Teemu Miettinen, MIT’s research scientist and lead author of research.

Professor Scott Manaris is the lead author of the study, and biotechnology students Kevin Lee and Alice Ram are co-authors.

Illustration of a typical animal cell.  Number 12 is the lysosome, an organelle that functions as a cell waste disposal system.

Measure mass

Normally, the dry mass of cells (the weight of the contents excluding water) is measured using a microscopy technique called a quantitative phase-contrast microscope. Although this technique can measure cell growth, it does not provide information on the molecular content of the dried mass and is difficult to use in cells that have grown suspended in a liquid.

Professor Manaris’s laboratory at the Massachusetts Institute of Technology had previously developed a technique for measuring the buoyant mass of cells, that is, the mass of cells when they float in a liquid such as water.

This method measures buoyant mass by pouring cells into a channel fixed to a vibrating cantilever, which is a connecting clamp. You can repeat this several times and monitor changes in the mass of a particular cell for hours or days.

For their new research, researchers wanted to adapt this technique so that it could be used to calculate the dry mass of cells and the density of that dry mass.

About 10 years ago, they had already discovered that the dry mass of a cell could be calculated by measuring the cell first with normal water and then with heavy water. A stable isotope of water with two deuteriums or deuterium atoms, protons and neutrons in the nucleus. You can then use these two measurements to calculate the dry mass of the cell.

Heavy water is toxic to cells

However, there was a problem with the method of calculating the dry mass. Heavy water is toxic to cells, so we could only get one measurement per cell. Last year, Miettinen set out to design a system that could repeatedly measure cells with minimal exposure to heavy water.

In the system he devised, cells are briefly exposed to heavy water as they flow through microfluidic (very thin) channels. Since the cell replaces its total water content in just one second, researchers should measure the mass of the cell when filled with heavy water and compare it to the mass of normal water to calculate its dry mass. I can.

“Our idea was that if we could minimize exposure to heavy water, we could configure the system to repeat this measurement for extended periods of time without damaging the cells,” Miettinen said. Says. “This allows us to monitor not only the dry mass of cells microscopically performed by other researchers, but also the density of dry mass, which provides information about the biomolecular composition of cells.”

Researchers have shown that their dry mass measurements are qualitatively consistent with previous quantitative phase-contrast studies. It not only gives the MIT team method a density of dry mass, but also allows for higher time resolution (more measurements in a short time), helping to reveal the dynamics of cells during mitosis. increase. This is a form of cell division. ..

An expression of a process called cytosis. Exocytosis is on the left side, the substance is excreted from the cell, and endocytosis is on the right side, and the substance is taken up by the cell.

Put out the garbage

Researchers have used new techniques to study cells that have undergone mitosis and what happens to the cell mass and cell composition in the process.

In a 2019 study, Miettinen and Manalis concluded that the buoyant mass increased slightly at the onset of mitosis. However, other quantitative phase-contrast studies have suggested that cells may retain their mass or lose their dry mass at the onset of cell division.

In a new study, the MIT team measured three types of cancer cells, which are easier to study because they divide more often than healthy cells. Surprisingly, they found that when they started the cell division cycle, the dry mass of the cells actually decreased. Its mass will be restored later before the split is complete.

Further experiments have shown that when cells initiate mitosis, the activity of a process called lysosomal exocytosis increases. Lysosomes are organelles of cells that break down or recycle waste products. Exocytosis is the process used to remove molecules that are no longer needed.

Researchers have also found that dry mass density increases as cells lose dry mass. As a result, they believe that cells lose low-density molecules such as lipids (substances like fat) and lipoproteins (specific proteins and compounds of lipids).

They assume that this process is used to remove toxic molecules before the cells divide. “What we’re seeing is that cells may be trying to dispose of damaged components before cell division,” says Miettinen.

Cancer and neurodegenerative diseases

Researchers explain why their findings are likely to cause non-dividing neurons and brain cells to accumulate toxins such as tau protein and beta-amyloid peptides that are associated with the development of Alzheimer’s disease. I think it will be useful.

Findings may also be related to cancer. Cancer cells use exocytosis to get rid of some chemotherapeutic drugs and help them become resistant. Theoretically, being able to prevent the development of exocytosis before cell division may help make cancer cells more sensitive to such drugs.

“Some diseases, such as neurogenic diseases, want to expand exocytosis, while others, like cancer, want to reduce exocytosis,” says Miettinen. “In the future, if we can better understand the molecular mechanism behind this and find a way to induce or inhibit exocytosis outside mitosis, it will be used to treat disease. There will really be a switch. ”

The Studies by Miettinen, Ly, Lam and Manalis eLife† This article is based on a press release from the Massachusetts Institute of Technology.

A complete photo from the top of the article on cells at various stages of cell division. Magenta represents DNA, green represents lysosomal markers on the cell surface, and lysosomal exocytosis.

Source: vrt


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