Scientists have uncovered how tissue engineering affects the movement of cells through the body, with potential applications in cancer research
(Santa Barbara, California) – Cells are constantly moving throughout our bodies, performing the myriad processes essential for tissue growth, immune responses, and general well-being. This clamor is guided by chemical indicators that scientists interested in cell migration have long studied.
To better understand this phenomenon, a team of biologists and physicists, led by Distinguished University of California Santa Barbara Professor Dennis Montiel, investigated the effect of biological ecology engineering on cellular locomotion. Using mathematical models and Drosophila, the group discovered that physical space has a significant effect on cell migration. Specifically, tissue engineering can create a less resistant pathway, which directs cellular motion. These ideas published in the magazine ScienceIt is a victory for basic research and can find applications in fields as diverse as oncology, neuroscience and developmental biology.
Directed cellular migration is an essential feature of biological processes, both normal and pathological. “Without directional cell migration, embryos would not develop, wounds would not heal, and the immune and nervous systems would not form and would not function,” said Montell, a professor of Dogan in the Department of Molecular, Cellular and Developmental Biology. “However, cell migration also contributes to inflammation and cancer metastases, so understanding the underlying mechanisms has gained much interest over the decades.”
Scientists have long known that cells sense chemical gravity. Many believed that a chemical attractive gradient was all that was necessary for cells to migrate to where they were needed. However, researchers are now increasingly looking at how the physical environment contributes to the way cells choose their pathways. However, this is a practical challenge, since reconstructing the engineering of living tissue in an artificial environment is challenging.
Montiel’s team experimented with fruit fly ovaries – one of the oldest and best models to study cell migration – to elicit the contributions of several different factors. Inside the ovary there are several egg chambers made up of 15 pathogen cells and one egg, or developing egg cell, at one end. The pathogen cells support the growth of the egg.
Approximately 850 follicular cells surround the pathogen and oocyte. Among these, a group of six to eight at the tip of the oocyte compartment, called boundary cells, separate and migrate between the pathogen cells to the oocyte, where they are crucial to the final development of the oocyte.
Not only does this system provide an ideal model to study cellular motility in general, the boundary cell mass behaves very similarly to metastatic carcinomas. “At first, the system might seem so mysterious and mysterious that it is picked out of the blue,” Montell admits, “but as it turns out, Mother Nature is reusing things, and the mechanisms that these cells use to move are very similar, even in molecular details, to how cancer cells move.” “
There are two components to border cell migration. They clearly move from the front to the back of the ovum chamber. However, what has been underestimated so far is that they also stay in a central location rather than moving into the perimeter of the room on their journey, despite there being nearly 40 different side paths that they can follow.
The researchers found that the chemical attractant could not explain the central pathway selection – another thing that should keep the boundary cells along their pathway. In fact, when they turned off the cells’ ability to detect chemical signals, the researchers found that the cells were still in the center of the oocyte compartment, even though they were no longer reaching the oocyte at the opposite end.
The egg chamber is filled with many cells, which presents a stacking problem much like the balls that are packed in a cage. Mathematicians have been solving problems like this for centuries and have found that there is more space in areas where more cells congregate. The team confirmed this by dipping the egg chamber in a fluorescent liquid that fills the gaps between the cells.
“The boundary cells seem to choose the center because it is a place where there is a little more space,” Montiel said. “The most surprising thing is that the physical space is so small, and much smaller than the things that you move through. It is this small space that makes the difference.”
Co-lead author Wei Dai, a former postdoctoral researcher in Montiel’s lab, carefully studied the oocyte chamber under a microscope and carefully rearranged the cells in a 3D model. This allowed the physicists on the project – Yuansheng Cao and Wouter-Jan Rappel of the University of California at San Diego and Nir Goff of the Weizmann Institute of Science in Israel – to create a mathematical model of the system on which the simulations would run.
Son Montiel, a technical director at Pixar Animation Studios, was able to superimpose the results of the mathematical model to the 3D recreation of the egg room. The results supported the hypothesis that the additional intercellular void space created the optimal pathway.
To ensure that the vault geometry was really responsible for the boundary cell pathway, another lead author of the paper Xiaoran Guo, PhD student in Montiel’s laboratory, looked at the mutant oocyte chambers with 31 pathogen cells, as opposed to the usual 15. In these in the most crowded cases, still Border cells choose a pathway through the region with the most cell junctions, rather than the physical center of the egg compartment.
“Tissue engineering creates a central pathway of least resistance, which provides directional information just as important as that provided by chemical attractants,” said Montell, adding that for 15 years chemical signals were thought to be the only directive signals.
You suspect a number of different factors that underlie the behavior of cells. While traveling, the boundary cells explore their surroundings by expanding small protrusions of the cell membrane, which are roughly the same size as the gaps between pathogen cells. In addition, the pathogen cells are compressed with proteins where they come into contact. By traveling through vacuoles where several cells meet, the boundary cells need not break all of these connections to slip.
The study results demonstrate that scientists need to consider the impact of the physical environment for all kinds of situations in which cells migrate across confined spaces; For example, the development of the brain or the movement of immune cells through lymph nodes and tumors.
“Getting immune cells into a tumor can be a challenge, and part of that may be the challenge of tissue engineering,” Montiel said. “Who would have thought what we really needed might be a tumor suppression to help immune cells enter.
“These results add a new understanding to the way we think about which cells are attracted to and how they move.”
Note to Editors: Denise Montell is available at [email protected] Xiaoran Guo is available in [email protected] Downloadable images can be found at TK.
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