Biochemical controls: the role of the interstitium (Introduction)

by David Turell , Friday, April 26, 2024, 18:08 (209 days ago) @ David Turell

Filling space, transporting proteins, creating actions:

https://www.the-scientist.com/interstitium-a-network-of-living-spaces-supports-anatomic...

"The human body is enmeshed in an intricate internal web of living spaces known as the interstitium.1 These fractal-like structures create a vast honeycomb network of fluid-filled openings within and between tissues and organs that spans the body and acts as a thoroughfare. A sophisticated system of connective tissue, including collagen and various other extracellular matrix proteins, supports the continuity of this network. The interstitium is increasingly being recognized as a fundamental anatomical structure and body-wide communication system.

“'It's actually not an organ. It's a system,” said Neil Theise, a medical doctor and professor of pathology at NYU Grossman School of Medicine, whose team made the discovery. “The space itself may be as large as 100 to 200 microns. It's grossly macroscopic, you can see it when you look at any connective tissue in the body, and you can pull it apart with tweezers. That’s not because the collagen easily shreds, but because it's actually a net,” said Theise.

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"When Theise and his colleagues made their ground-breaking discovery in 2018, they realized that the spaces in living tissue corresponded with the cracks routinely seen in fixed tissue sections on microscope slides. “It turns out those are the remnants of the living spaces,” Theise said.

"With this realization, the cracks in contemporary science and medicine were exposed. Despite the vast scientific knowledge that exists about the human body, the picture remains profoundly incomplete....The interstitium may be the missing piece of the puzzle that helps explain the interconnectivity between every cell, tissue, organ, and hidden crevice in the body. “There isn’t a tissue that isn’t riddled with the spaces. The interstitium has the ability to communicate through the body across every scale, from the quantum electromagnetic level, all the way up to the cellular level,” Theise said.

"Because the interstitium is a fibrous network, mechanical stimuli that affect a fiber in one area also affect other regions of the body, creating a network of mechanical connectivity. "If you want to communicate a signal, mechanics are so efficient,” said Andrew Pelling, a professor of physics and biology at the University of Ottawa. “It's no surprise that there are all these highly evolved systems to sense and transmit mechanical information."

"These explained further that the collagen that makes up the interstitium is piezoelectric.2,3 It can convert mechanical force into electrical currents that may carry charged molecules through the interstitium. “Collagen, when you stack it up high enough, becomes a piezo crystal. Any movement of the collagen will generate electrical energy,” Theise said. This may have far-reaching implications from tissue and organ regeneration to gastrointestinal function.

"The interstitium also acts like a sieve in other ways. The spaces of the interstitium are filled with hyaluronic acid, which has a high capacity to hold water, creating a gel. Hyaluronic acid is also highly charged, meaning it can preferentially allow access to certain molecules depending on their charges. In doing so, the interstitium has the potential to modulate the movement of large and small molecules, as well as cells. Although it is not clear how and where they move, the mechanisms may relate to signaling molecules like growth factors, chemokines, and cytokines that create chemical gradients to guide movement. This is particularly relevant for cell migration in the context of cancer cell metastasis through the interstitium.7 “I can show you a tumor marching through these spaces,” Theise said, referring to histopathological tissue slides of cancerous tissue. The interstitium is also believed to be involved in sepsis and fluid balance.

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"'It makes sense to me, at least conceptually, that it is such an important space. It's everywhere, it's the interface between all of these discrete systems,” Pelling said. “Biology doesn't tend to create structures that are not important in some way. It's the same as those older notions about junk DNA that are starting to crumble. Biology is extremely efficient."

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"Understanding how the interstitium works will define more of the rules about how the trillions of cells in the human body communicate across vast distances to create the exquisitely complex system that is the body. How these things all add up are vast scientific questions that will require a meticulously reductive approach as well as cultivation of a beginner’s mind. “If you do any kind of work with dedicated focus, the secrets of the universe are there in what you're doing,” Theise said."

Comment: our body is 90% water! This is where much of it is held. It is amazing we missed for so long this important part of the body and how it functions. Now that it is seen it explains the liquid content of our body is used for integrated functions of all parts.