A study reveals physical onions that oocytes are responsible for growing large

Egg cells are the largest cells produced by most organisms. In humans, they are several times larger than normal body cells and about 10,000 times larger than sperm cells.

There is a reason that egg cells, or oocytes, are so large: They need to accumulate enough nutrients to support an embryo that grows after fertilization, as well as mitochondria to power all that growth. However, biologists still do not understand the whole picture of how egg cells grow so large.

A new study in fruit flies, by a team of MIT biologists and mathematicians, reveals that the process by which the oocyte grows rapidly and rapidly before fertilization is dependent on physically similar onions. gases between balloons of different sizes.

In particular, the researchers showed that “nurse cells” around the larger oocyte dump the contents into the larger cell, just as air flows from a smaller balloon to a larger one. when connected by small tubes in an experimental position.

The study shows how physics and biology come together, and how nature can use physical processes to create this powerful mechanism. If you want to develop as an embryo, one of the goals is to make things very reproducible, and physics provides a very robust way to achieve specific transport processes. “

Jörn Dunkel, Associate Professor, Applied Physical Mathematics, Massachusetts Institute of Technology

Dunkel and Adam Martin, an associate professor of MIT biology, are the main authors of the paper, which appears this week in the Proceedings of the National Academy of Sciences. The lead authors of the postdoc study are Jasmin Imran Alsous and graduate student Nicolas Romeo. Jonathan Jackson, a graduate student of Harvard University, and Frank Mason, a research assistant professor at Vanderbilt University School of Medicine, are also authors of the paper.

Physical process

In female fruit flies, eggs develop inside cell clusters called cysts. An unopposed oocyte passes through four cycles of cell division to produce one egg cell and 15 nurse cells. However, the cell separation is infinite, and each cell remains connected to the others by narrow channels that act as valves that allow material to pass between cells.

Members of Martin’s lab began studying this process because of their longstanding interest in myosin, a class of proteins that can act as motors and help contract muscle cells. Imran Alsous performed live, high-performance images in egg formation in fruit flies and found that myosin does indeed play a role, but only in the second stage of the transport process.

At the earliest stage, the researchers were puzzled to see that the cells did not appear to increase their contractile capacity at all, suggesting that equipment other than “pressure” was beginning to develop. transport.

“Both levels are very obvious,” says Martin. “After we saw this, we were told, because of course there is no change in myosin associated with the beginning of this process, which is what we were expecting to see.”

Martin and his lab then teamed up with Dunkel, who studies soft surface physics and flow material. Dunkel and Romeo questioned whether the cells could behave in the same way that balls of different sizes behave when connected. While it may be expected that the larger balloon would emit air to a minimum until they are the same size, what actually happens is that air flows from the the smallest to the largest.

This happens because the smaller balloon, which has a larger curvature, receives more surface tension, and therefore a higher pressure, than the larger balloon. So air is taken out of the smallest balloon and into the largest one. “It’s counterintuitive, but it’s a very robust process,” Dunkel says.

Modifying previously identified mathematical equations to explain this “two-balloon effect,” the researchers came up with a model that describes how the content of a cell is transfer from the 15 small nurse cells to the large oocyte, based on their sizes and connections. together. The nurse cells in the layer closest to the oocyte move the contents first, and then the cells in further layers.

“After spending some time building a more complex model to explain the 16-cell problem, we realized that the simulation of the simplest 16-balloon system looked very similar to the 16-cell network. .It is surprising to see such a contradiction but simple mathematical ideas describe the process as well, “Romeo says.

The first stage of nurse cell dumping appears to occur when the channels that bind the cells become large enough for cytoplasm to move through. As soon as the nurse cells shrink to about 25 percent of their original size, leaving them just slightly larger than their nuclei, the second stage of the process is stimulated and myosin shortening takes place. the remnants of the nurse cells enter the egg cell.

“In the first part of the process, there is very little pressure going on, and the cells just shrink evenly. Then this second process starts towards the end where you will start to push more actively, or deformations like peristalsis in the cell, which will end the dumping process, ”says Martin.

Cell interaction

The findings show how cells can coordinate their behavior, using both biological and physical devices, to produce behavior at the tissue level, Imran Alsous says.

“Here, you have several nurse cells and their job is to nurture the egg cell in the future, and to do that, it seems that those cells are carrying the contents in a co-ordinated way. directed and directed to the oocyte, “she says.

Oocyte appearance and early primary development in fruit flies and other invertebrates are similar to those of mammals, but it is not known whether the same mechanism of egg cell growth is seen in humans or other mammals, the researchers found. saying.

“There is evidence in mice that the oocyte develops like a cyst with other interconnected cells, and that there is some transport between them, but we don’t know if the devices we see here work in mammals, “says Martin.

The researchers are now investigating what stimulates the second, myosin-powered phase of the dumping process. They also investigate how changes in the original sizes of nurse cells may affect egg formation.