The human body, a marvelous and complex biological machine, is composed of approximately 60 percent water. Although it is well-known that water is crucial for life, its distribution and role within our tissues are much more complex than was previously thought. More than half of this water is located within the cells themselves, but a significant portion, long neglected by science, fills the microscopic spaces between them. This so-called intercellular or interstitial fluid, much like the sea that fills the space between grains of sand on a beach, has proven to be a key factor in determining the physical properties of our organs and tissues.

Engineers from the prestigious Massachusetts Institute of Technology (MIT) have made a stunning discovery that fundamentally changes our understanding of biology and tissue mechanics. Their study, published on June 21, 2025, in the esteemed scientific journal Nature Physics, revealed that it is this extracellular fluid that plays a crucial role in how tissues behave under physical pressure. This discovery opens up entirely new perspectives in the research and treatment of conditions such as aging, cancer, diabetes, and various neuromuscular diseases.

A Revolution in Understanding Tissue Mechanics

When a tissue is pressed, squeezed, or deformed in any way, its ability to adapt, or its pliability, directly depends on the ease of fluid flow between the cells. Research by the team from Cambridge has shown that tissues become softer and relax more quickly, that is, return to their original state, when the flow of interstitial fluid is unobstructed. On the other hand, when cells are densely packed, leaving little space for fluid flow, the tissue as a whole becomes stiffer, harder, and significantly more resistant to deformation. This insight represents a significant departure from previous scientific dogma.

Conventional wisdom had, for decades, assumed that the mechanical properties of tissues, such as elasticity and strength, primarily depend on intracellular structures – the cytoskeleton, proteins, and other components within the cell itself. The influence of the environment surrounding the cells was largely underestimated or completely ignored. Now, thanks to the work of scientists at MIT, it is clear that intercellular flow is a key mechanism that determines how tissues will physically react to forces from the environment. This concept, known as poroelasticity, is applicable to a wide range of physiological processes and conditions. It helps us understand how muscles endure strain during exercise and recover from injuries, but also how the physical adaptability of tissues can affect the progression of aging, the spread of tumor cells, and the development of other medical conditions.

The Experimental Approach: How Water Became the Star of the Research

To confirm their hypothesis, scientists led by Professor Ming Guo and the study's lead author, Dr. Fan Liu, conducted a series of sophisticated experiments. Their interest in this topic was sparked by an earlier study from 2020, in which they observed how fluid flows from the center of a tumor towards its edges through crevices between individual tumor cells. They then discovered that pressure on the tumor increases this intercellular flow, creating a kind of "conveyor belt" that can help spread metastases. This led them to question whether this flow plays a similar role in healthy, non-cancerous tissues.

"It became obvious that the ability of fluid to flow between cells has a huge impact," explains Guo. "So we decided to expand our research beyond tumors to see how this mechanism affects the reaction of other tissues to deformation."

For the research, the team analyzed various types of biological tissues, including cells derived from the pancreas. In the laboratory, they grew small clusters of tissue, so-called spheroids, each less than a quarter of a millimeter in diameter and consisting of about ten thousand individual cells. To test these microscopic samples, the team had to construct a completely new, custom device. "These microtissue samples are in a 'sweet spot' – too large to be observed with atomic force microscopy techniques, and too small for standard, larger material testing devices," explained Guo. "That's why we had to build our own."

Their innovative device combined an ultra-precise microbalance, which can measure minute changes in weight, with a stepper motor capable of pressing the sample with nanometer precision. The procedure was as follows: a tissue cluster would be placed on the balance, and the motor would then press it in a controlled manner, flattening it from a spherical shape into a pancake-like shape. During this process, the balance recorded the change in the tissue's weight as it relaxed, and cameras filmed the entire deformation process. A key part of the experiment was testing clusters of different sizes. The researchers hypothesized that if the tissue's reaction was conditioned by fluid flow, larger clusters would take longer for the fluid to drain through them, and therefore would take longer to relax. If, however, the reaction depended solely on the internal structure of the cells, the relaxation time should be the same regardless of the sample size.

The results were unequivocal. In a series of experiments with different types and sizes of tissues, they observed a clear and repeatable trend: the larger the cluster, the longer it took to relax. This was the crowning proof that intercellular fluid flow dominates the mechanical reaction of tissue to deformation. Scientists from the University of Beijing also participated in the research, confirming the global relevance of this discovery.

Implications for Medicine and Future Therapies

The discoveries from the MIT lab, located in the city of Cambridge, have far-reaching implications for practical medicine. The team of scientists believes that the results could be applied to understanding a wide range of physiological conditions. For example, with aging, tissues become stiffer, partly due to changes in the extracellular matrix that hinder fluid flow. In cancer, increased pressure within a tumor can drive intercellular flow that literally "pushes" cancer cells into the surrounding healthy tissue, promoting invasion and metastasis. Understanding this mechanism could lead to new strategies for preventing the spread of the disease.

The team's vision extends to the design of artificial tissues and organs. When engineering artificial tissue for transplantation, scientists could optimize intercellular flow to improve its function, resilience, and integration into the recipient's body. They also suspect that this flow could be used as a new pathway for delivering nutrients or drugs, either to heal damaged tissue or to target and destroy tumors. "As our work shows, applying pressure to tissue stimulates fluid flow," says Guo. "In the future, we can think about designing methods, such as therapeutic massage, to purposefully direct fluid flow to transport nutrients between cells."

The next step for this research team is to investigate the role of intercellular flow in brain function, with a special focus on neurodegenerative disorders like Alzheimer's disease. "Intercellular or interstitial flow in the brain helps to remove metabolic waste products and deliver nutrients," adds Liu. "Improving this flow in certain cases could be beneficial, for example, for clearing the amyloid plaques that are characteristic of Alzheimer's disease." This fundamental discovery about the importance of the space between cells opens a new chapter in biology and medicine, promising progress in areas that were until recently unimaginable.

Source: Massachusetts Institute of Technology