Cells change tension to make tissue barriers easier to get through

A new mechanism by which signaling molecule can act in fruit flies.

Cells change tension to make tissue barriers easier to get through
Image: Ist Austria

Like modest building blocks, billions of cells form our bodies. In any case, not at all like building obstructs, a few cells can move around the body. This is vital amid development, yet additionally when the resistant framework battles diseases.

The most notorious cell movement occurs during metastasis when cancer cells spread from a primary tumor. To move around the body, some cell should have the capacity to get from one tissue into another – for instance, when an immune cell needs to escape the vein and into harmed or inflamed tissue.  But some tissue barriers are made of cells that sit closely together, like a tight wall, making it hard for migrating cells to get through.

In a new study, scientists at the IST Austria reported that in the fly, a type of immune cell called a macrophage has an easier time squeezing through when a signal is sent to change the tension of the cells within the wall. The cells squeeze through tissue barriers in the body better when these barriers are made less stiff.

Daria Siekhaus, Professor at the Institute of Science and Technology (IST Austria) said, “We have found a new mechanism by which the movement of cells through tissue barriers is made easier.”

Scientists analyzed the movement of macrophages in the fruitfly Drosophila melanogaster. Macrophages play a vital role in development, and in responding to wounds, infections, or other threats to the organism, migrate through the developing fruit fly embryo.

In addition, they have to get through a tissue called the germband. The researchers found that migrating macrophages stall when they reach this barrier. They invest energy endeavoring to push their way in, a task that is made less demanding by a flag sent to the phones of the hindrance that decreases their strain. This adjustment in pressure makes the hindrance cells not so much firm but rather more deformable, enabling macrophages to all the more effortlessly crush between them.

Scientists discovered that this signal which tells the tissue barrier to be softer is Eiger. It is a Drosophila form of tumor necrosis factor (TNF), a signaling molecule that is important for inflammatory signaling in vertebrates. Binding to its receptor Grindelwald, Eiger changes the localization of another protein, Patj, that controls the activity of Myosin, a motor protein essential for generating and maintaining cellular tension.

To demonstrate their speculation, scientists used a method that has been created already, called laser ablation, to slice through the edge of the cells under a microscope. Like when an elastic band snaps and the closures move far from each other the cut edges of the cell isolated. The greater the tension in a rubber band as it snaps, the faster the ends spring apart.

The same applied to the cells. By quantifying the speed of separation, the researchers can calculate how much tension the cell was in the first place. In mutant embryos, in which no Eiger molecule signals to the barrier cells, Myosin activity in the cells is higher and the cells snap apart quicker than in wild-type cells, i.e. they are under more tension.

Daria Siekhaus explained, “When tension in surrounding cells is higher, immune cell migration across the barrier is reduced. We have shown the physical effects of these molecular changes, and have defined a new pathway by which a TNF can act.”

Aparna Ratheesh, the first author of the study, is excited by the active process of invasion they identified: “Macrophages squeeze between cells. In doing so, they force their way into a place and shape the surrounding tissue. This pushing has to be controlled and directed, and leads to an active invasion.”

Siekhaus reported, “As TNF signaling molecules also play an important role in vertebrates, their results potentially have importance beyond the fruit fly. We have some data that TNF plays a role in the migration of immune cells during the development of vertebrates. So our results may also be important in the vertebrate context.”

The study is published in Developmental Cell.