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How tissue shape affects the movement of cells through the body-ScienceDaily

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Cells constantly move throughout our body, performing a myriad of operations that are important for tissue development, immune response, and general health. This hustle and bustle is guided by chemical cues that have long been studied by scientists interested in cell migration.

To better understand this phenomenon, a team of biologists and physicists led by a prominent professor at the University of California, Santa Barbara, investigated the effects of the shape of the biological environment on cell movement. did. Using mathematical models and fruit flies, the group discovered that physical space has a profound effect on cell migration. That is, the shape of the tissue can create the least resistance pathways that guide the movement of cells.These insights published in the journal ScienceIs a victory in basic research and has the potential to find applications in a variety of fields such as oncology, neuroscience and developmental biology.

Directed cell migration is an essential feature of both normal and pathological biological processes. “Without directional cell migration, embryos do not develop, wounds do not heal, and the immune and nervous systems do not form or function,” said Professor Dagan of the Department of Molecular, Cellular, and Developmental Biology. One montel says. “But cell migration also contributes to inflammation and cancer metastasis, so understanding the underlying mechanism has been of considerable interest for decades.”

Scientists have long known that cells sense chemical attractants. Many thought that all that was needed for cells to move where they were needed was a gradient of chemical attractants. However, researchers are now increasingly looking at how the physical environment contributes to the way cells choose pathways. However, this presents practical challenges because reconstructing the shape of living tissue in an artificial environment is a difficult task.

Montel’s team experimented with the Drosophila ovary, one of the earliest and most well-studied models of cell migration, to elicit the contribution of several different factors. Within the ovary are several oocytes, consisting of 15 nurse cells and an oocyte, or a developing egg cell. Nurse cells support egg growth.

Approximately 850 follicle cells surround the nurse and oocytes. Of these, 6 to 8 groups at the tip of the oocyte, called boundary cells, separate and migrate between oocytes to the oocyte. In oocytes, it is important for the final development of the egg.

Not only does this system provide a perfect model for studying general cell motility, but boundary cell clusters behave very much like metastatic cancer. “At first, the system may look very vague and esoteric,” Montel admits. “But after all, Mother Nature reuses things, and the mechanism these cells use to move is the molecular details, how cancer cells move.”

Boundary cell migration has two components. They clearly move from the front to the back of the oviduct. However, what hasn’t been much appreciated so far is that despite the availability of about 40 different sidepaths, it remains centered rather than moving around the chamber during the move. ..

Researchers have found that chemical attractants cannot explain the choice of central pathways-something else must maintain boundary cells along those pathways. In fact, when knocking out the cell’s ability to detect chemical signals, researchers found that the cell remained in the center of the oocyte, but did not reach the contralateral oocyte. ..

Since the egg chamber is filled with many cells, it causes stacking problems similar to packing balls into a crate. Mathematicians have been working on such problems for centuries, but have found that there is more space in areas where more cells gather. The team confirmed this by immersing the egg chamber in a fluorescent solution that fills the gaps between cells.

“It seems that the border cell is choosing the center because it’s a bit more space,” says Montel. “The most surprising thing is that the physical space is really small, much smaller than the objects that move through it. It’s this small space that makes the difference.”

Weidai, a former postdoctoral researcher in Montel’s lab, co-author, carefully studied the egg chambers under a microscope and carefully reproduced the cell placement in a 3D model. This allowed the project physicists (Yuansheng Cao and Wouter-Jan Rappel at the University of California, San Diego, Nir Gov at the Weizmann Institute of Science in Israel) to create a mathematical model of the system to perform the simulation.

Later, Montel’s son, technical director of Pixar Animation Studios, was able to overlay the results of the mathematical model on the 3D recreation of the egg chamber. The results supported the hypothesis that the extra space between cells created the optimal path.

To confirm that the cellar shape is actually involved in the border cell pathway, the other lead author of this treatise, Xiaoran Guo, a PhD student in Montel’s lab, has 15 regular pieces. Instead, we examined a mutant ovary with 31 nurse cells. Even when more congested, the boundary cells chose a pathway through the region with the most cell junctions rather than the physical center of the oviduct.

“Tissue shape creates a central pathway with minimal resistance and provides as important directional information as that provided by chemical attractants,” said Montel, who said that chemical signals are the only guidance for 15 years. He added that it was thought to be a clue.

She suspects various factors that underlie the behavior of cells. During migration, boundary cells explore their surroundings by stretching small protrusions on the cell membrane. This is about the same scale as the gap between nurse cells. In addition, nurse cells are compressed with proteins where they come into contact. By passing through the gap where several cells meet, the bounding cells do not have to break through all these joins.

The results of this study show that scientists need to consider the effects of the physical environment in all kinds of cases where cells move in tight spaces. For example, brain development and the movement of immune cells through lymph nodes and tumors.

“Immune cells can be difficult to get into a tumor, and perhaps part of it is a matter of this tissue shape,” Montel said. “Who would have thought that what we really had to do was probably loosen the tumor and help the immune cells invade.

“These discoveries add a new concept to our thinking about how cells are attracted and move around.”

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