Water makes about 60 percent of the human body. More than half of this water revolves around the cells that make organs and tissues. Most of the remaining water flows between the cells in the nook and crane, like sea water between sand grains.

Now, MIT engineers have found that this “intercellular” fluid plays a major role of how the tissues are squeezed, pressed, or react when they are physically deformed. Their findings can help scientists understand how cells, tissues and organs are physically adapted to conditions such as aging, cancer, diabetes and some neuromuscular diseases.

Shown in a paper Nature physicsResearchers suggest that when a tissue is pressed or squeezed, it is more obedient and relaxes more quickly when the fluid between its cells easily flows. When the cells are packed simultaneously and there is less space for interconnect flows, the tissue stifer is as a whole and is pressed or squeezed.

Conclusions challenge traditional knowledge, which has assumed that compliance with a tissue mainly depends on what is, instead of a cell, what is there. Now that the researchers have shown that intercellular flow determines how adapted to physical forces, the results can be applied to understand a wide range of physical conditions, in which how muscles face exercise and recover from injury, and the physical adaptation of a tissue can affect the progression of aging, cancer and other medical conditions.

The team said the results can also inform the design of artificial tissues and organs. For example, in engineering artificial tissue, scientists can adapt to interconnect flows within the tissue to improve their function or flexibility. Researchers suspect that intercellular flow may also be a path to distribute nutrients or treatments, either to fix a tissue or to eradicate tumors.

People know that tissues have a lot of fluid between cells, but how important is especially in tissue deformation, is completely ignored. Now we really show that we can inspect this flow. And as the tissue is deformed, the flow between cells dominates the behavior. So, let’s note this when we study diseases and engineer tissues. ,

Associate Professor of Mechanical Engineering at Ming Guo, MIT

Guo is a co-writer of the new study, including lead author and MIT Postdock Fan Liu PhD ’24, as well as Bo Gao and Hui Lee Lee of Beijing Normal University and Liran Lei and Shunan Liu of Peking Union Medical College.

Suppressed and squeezed

Tissue and organs in our body are undergoing persistent physiological deformity, large stretch of muscles during motion and small and stable contractions of the heart during stress. In some cases, how easily tissue may be adapted to deformation, may be related to how quickly a person can overcome, for example, an allergic reaction, a sports injury or brain stroke. However, in fact that determines the reaction to the deformation of a tissue is largely unknown.

Guo and their groups in MIT saw in the mechanics of tissue deformation, and especially the role of narrative flow, after a study published in 2020. In that study, they focused on the tumor and the way the fluid can flow out of its sides from the center of a tumor, cracks and individual tumor flowing through the cells. They found that when a tumor was squeezed or pressed, the intercellular flow increased, served as a conveyor belt to transport fluid from the center to the sides. The interconnect flow, they found, can fuel tumor invasion in the surrounding areas.

In its new study, the team noticed what role this interconnect flow could play in other, non -non -exists.

,Whether you allow the fluid to flow between cells or not, “Guo says.” So we decided to look beyond the tumor how this flow affects how other tissue reacts to deformity. ,

A liquid pancake

Guo, Liu, and their colleagues studied interconnect flows in a wide variety of biological tissues, including cells obtained from pancreatic tissue. He conducted experiments in which he first cultured small groups of tissue, each of which measures less than one millimeter wide and less than thousands of individual cells. He placed each tissue cluster in a custom-designed test platform, which was specially created by the team for studies.

“These microscopic samples are in this sweet field where they are very large to look with atomic force microscopy techniques and are very small for bulkier devices,” says Guo. “So, we decided to make a device.”

Researchers optimized a high-stake subtlety that measures minus changes in weight. They paired it with a step motor, designed to press on a sample with nanometer precision. The team placed the tissue cluster at a time on the balance and recorded the changing weight of each cluster as it rested in the shape of a pancake in response to compression with a shell. The team also took videos of the cluster, as they were squeezed.

For each type of tissue, the team formed groups of different -sizes. He argued that if the tissue response is governed by the flow between cells, the larger the tissue should be taken to leak through the water for as long as it is, and therefore, the tissue should be taken to relax for a long time. Regardless of size, the amount of the same time should be taken if the reaction of the tissue is determined by the structure of the tissue instead of the fluid.

On many experiments with different types of tissue types and sizes, the team observed a uniform trend: The longer the cluster is, the longer the time to relax, shows that the intercellular flow dominates a tissue reaction to deformation.

“We show that it is an important component to consider the basic understanding of intercellular flow tissue mechanics and also in engineering living systems,” says Liu.

Moving forward, the team planned to see how narrative flow affects the function of the brain, especially in disorders such as Alzheimer’s disease.

“Intercellular or interstitial flow can help you remove waste and give nutrients to the brain,” is called Liu. “In some cases it can be a good thing to increase this flow.”

“As it shows the work, as we apply pressure to a tissue, fluid will flow,” says Guo. “In the future, we can think of designing ways to massage a tissue to allow fluid to transport nutrients among cells.”

The work was supported by the Mechanical Engineering Department in MIT.