The Interstitium

Author: R. Paul Lee, DO, FAAO, FCA
March, 2024

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Let’s explore why the interstitium is so vital to osteopathy. In 2018, researchers claimed to have discovered a “new organ” in the body – the interstitium.[1] As histologists, they realized that they had been overlooking this “organ” because of fixation techniques that turned this fluid-filled space into a tight-looking collagen band under the light microscope. Using advanced in vivo technology (Probe-based Confocal Laser Endomicroscopy), they discovered that indeed the interstitium is fluidic and vital. In their paper, they commented that the interstitium has multiple functions that they previously didn’t recognize in both health and disease. They indicated that the interstitium serves cells by delivering nutrients, cell signaling molecules, cytokines, hormones, etc. as well as providing the fluid to form lymph. It also may play a role in metastasis of cancer and could contribute to disease, in general.  

As osteopaths, we have a fundamental understanding about fascia from our founder, A. T. Still, because it is philosophically formative and basic to our manual methods. And we are happy to have others confirm fascia’s seminal contribution to the structure and function of the organism. Since Dr. Still, we have endorsed the concepts that these modern histologists have recently recognized. Osteopaths refer to this tissue in the interstices between the cells as the interstitium or the extracellular matrix, which connects everything to everything.

In her book,[2] Jane Stark, DOMP extensively reviews the subject from the osteopathic perspective. She indicates that Dr. Still included in his conception of fascia tough structural bands such as the lumbodorsal fascia as well as its finer, intercellular, interconnecting aspect, and furthermore, its spiritual aspect – the dwelling place of the soul. Dr. Still awarded the fascia with a status significant enough to say, “By its action we live, and by its failure we shrink, or swell, and die.”[3] He said, “…he has seen by thought the frame work of life the dwelling place on which life sojourns? He feels that he can find all disturbing causes of life, the place that diseases germinate and grow, the seeds of disease and death.”[4] Fascia “carries to the mind of the philosopher the evidence, absolute, that it is the ‘material man,’ and the dwelling place of his spiritual being. It is the house of God, the dwelling place of the Infinite so far as man is concerned.”[5]

Despite Dr. Still’s elevated characterization of fascia, anatomy and physiology texts pay scant attention to osteopathy’s all-important matrix. Nevertheless, surgeons find fascia essential in guiding their dissections during surgery, thereby acknowledging that fascia delineates anatomy. We osteopaths recognize that fascia not only defines such anatomic landmarks, but simultaneously connects the entire organism into one functional unit.  Each compartment distinguishes itself by a specific function it contains: Glisson’s capsule around the liver – nutrient metabolism and storage, the pleura around the lung – air/blood exchange, or the dura mater around the brain – nerve communication. Simultaneously, fascia connects each division to everything else by its unifying characteristics. Fascia assures each compartment has ample and correct provisions to manage its specific tasks while at the same time informing it about what is going on elsewhere.

Fascia’s quality of connectedness can be attributed in large measure to the fibroblast, that cell that is characteristic of fascia and produces all its components. The fibroblast manufactures collagen and other structural proteins in addition to the metabolically active glycoproteins both of which convey information through mechanical vibrations and chemical and electrical transmissions. Through fascia’s watery bath and the fibroblasts’ fibrous products instantaneous gossip is spread from one end of the system to the other. But fibroblasts perform another important function to connect everything together: the cells themselves form a syncytium. Each fibroblast has cellular processes, like arms and hands reaching out to touch other hands, relaying cellular fluids and information through vibration and electrochemical signals. The fibroblasts’ internet instantaneously transmits from one end of the organism to the other.

The interstitium or extracellular matrix (ECM) contains the totality of tissue external to parenchymal cells. Structural proteins, primarily collagen, supply a sturdy scaffolding (collagen is as strong as steel) to support the matrix and its contents: nerves, vessels and cells. These structural proteins have much less attraction for water than the negatively charged field surrounding the glycoproteins. Most of the fluid in the ECM flows between the crevices formed by collagen. In these channels, water carries the essential substances of life that cells demand, e.g.: glucose and oxygen. Via the fluid in the adits among cells, connective tissue offers the multicellular organism all that the sea once provided when only single cells existed. It delivers nutrients from capillaries and conveys waste to the terminal lymph channels keeping the cells’ environment consistently healthy throughout as the sea once did.

Fascia acts like shrink wrap to cover everything inside the skin: bones (periosteum), muscles (perimysium), nerves (perineurium), and organs (Glisson’s capsule or dura mater). Inside the strong outer layer of structural proteins are more malleable and water-filled fibers. These long filaments (glycoaminoglycans like hyaluronan) with brush-like attachments (proteoglycans) binds water in large volumes to the surrounding field of significant negative charge from sulfated chondroitin and keratin. Glycoaminoglycans and proteoglycans operate within the gel-like, watery compartments of the structural protein scaffolding to provide a changeable environment to match the immediate demands of life and maintain a status of pristine health. These fibrous elements of the ground substance determine the viscosity of the matrix: more or less gel-like, through polymerization and depolymerization, respectively. This compliant viscosity works hand in glove with to and fro charge and flow of water, manifesting as a palpable fluctuation of fluid in the tissues.

This oscillating flow in the ECM delivers waves of nutrients from the capillaries to the parenchymal cells.[6]^,[7] Ions cyclically flow in the water, generating an EMF, while electrons flow along semiconducting (precise electron sharing) and piezoelectric (electro-mechanical transducing) fibers that close electric circuits.[8] ATP production has been shown to oscillate in the cerebral cortex[9] and we know that glycolysis is cyclical in other life forms, like yeast, for example.[10] This is evidence for the oscillation of intracellular metabolic functions from oscillating influences outside the cell. Waves of charge, changing pH, electrolyte concentration (Ca⁺⁺ waves)[11] and nutrient density fluctuate in the watery space between the cells. Through tensegrity (tensional integrity), mechanotransduction via integrins (special plasma membrane receptors) transmit this oscillating influence in the ECM to effect cyclical metabolism inside the cell.[12]

Even though it lies exterior to the metabolic processes inside the cell, the ECM commands regulatory control over the cell’s mechanisms of energy production, cell division, migration, and apoptosis. The cell membrane contains multiple cell receptors, including integrins, to connect the exterior with the interior of the cell. With these connections, the cytoskeleton reacts to the information conveyed during waves of decreased viscosity of the ECM and transmits it to the interior where it sends other signals to the mitochondria and nuclear genetic material.

With each cycle, the cell volume contracts expelling intracellular fluid into the extracellular space.[13] This corresponds to the inspiratory (flexion) phase of primary respiration in which the volume of CSF and other extracellular fluids increases. The fluid of cellular waste can then flow into the terminal lymphatic vessels to eventually be returned to the venous circulation or return directly to the local venous capillaries. Lymph is the product of this extracellular fluid with contributions from both intracellular and capillary fluids.

Much of the information transmitted through the ECM from capillaries to the parenchymal cells is in the form of vibration, but chemical and electrical signals are also essential. Some of the information also comes through nerve impulses and some from the capillary supply of nutrients. Still said the nerves control the vessels which send the building blocks for the body.[14] Stimuli from immune (cytokines) and endocrine (hormones) systems induce cellular responses via the fluid between cells. Both the gastrointestinal system, through the liver’s regulatory effects, and the pulmonary system through its autonomic control suffuse the blood with glucose and oxygen that the ECM receives from the capillaries and delivers to the cells. These are delivered through the blood by the heart, which has its own story to tell. It delivers messages in the form of waves of mechanical (sound) and electromagnetic energy with varying frequency and intensity according to physiological demands, regulated by the autonomics.

The magnetic field of the heart is the largest in the body, by far, and all tissues respond to its magnetic message. The magnetic field exceeds the boundary of the physical body assuring that the entire organism receives the periodic impulses. The nervous system provides the other electrical impulses to inform the ECM. Action potentials stimulate synapses to release their neurotransmitters to their target effectors. But, of premier interest is the function of the perineurium, a fluid-filled Schwann Cell wrapping of the peripheral nerves. Rather than expressing a digital (on/off) electric current of the action potential through depolarization of the axon’s plasma membrane, the perineurium expresses an analog direct current, continuously variable, which surrounds the plasma membrane. Robert O. Becker, MD[15] discovered an oscillating direct current within the perineural fluid. The perineurium is to the peripheral nervous system what the subarachnoid space is to the central nervous system. Both of these continuous spaces contain extracellular fluid, CSF, with an oscillating charge.

These two compartments are lined by specialized fascial cells, in the periphery by Schwann cells (they form myelin when tightly wrapped) and in the central nervous system by leptomeningeal cells (pia mater and arachnoid). The fluid within the compartments is specialized so as to nurture and protect nerves, providing the same environment for axons, dendrites and cell bodies throughout the entire nervous system. The oscillating electric potential in the CSF around the central and the peripheral nervous systems oversees the activities within their confines.[16]^,[17] The fluctuating charge transmits the Breath of Life that vivifies the tissue it touches and by proxy all the tissues through the aforementioned fascial interrelationships.

Furthermore, an oscillating current exists in the circulating blood. James Oschman[18] proposes that this oscillation is picked up by the blood due to its extensive exposure to the oscillating charge in the brain and CSF. This oscillation could be what Traube and Hering independently discovered in the mid 1800s in carotid arteries of dogs. The Traube-Hering wave is measured as an oscillation of arterial blood pressure that is slower than the cardiac pulse and independent from pulmonary respiration. Its rate corresponds to the oscillation in the brain and the perineural space and the fluctuation felt in the tissues, which is produced by oscillations in the extracellular fluid, the CSF. All of these oscillations, as predicted by William Sutherland, DO are manifestations of the Breath of Life.

According to the Intelligence of the Tide, as revealed by Primary Response Testing (PRT),[19] the “Breath of Life is a force field from non-material reality that impacts material reality by engaging and governing the behavior of charge.” The zero-point field exists wherever material substance does not exist, so sometimes it is referred to as the vacuum energy. This energy outside of physical form (made of atoms and its components), consists of virtual particles vibrating in a maelstrom of potential. This chaotic tumult occasionally creates real particles when by chance, virtual vibrations coincide to produce a positive interference pattern that exceeds the energetic threshold to emit a real photon, electron, neutron or proton. With this activity of the zero-point field we witness the formation of the building blocks of material reality. These real elementary particles are momentarily available for chemical and physical reactions in our everyday existence unless they return in a split second to the pure energy of the zero-point field before they might be utilized.

Dr. Sutherland borrowed from the creation story in the Bible: “And God formed man of the dust of the ground and breathed into his nostrils the breath of life, and man became a living soul.” [Genesis 2:7] We can see from Sutherland’s use of this term, the “Breath of Life,” that he was referring to the life force as the instigator for this oscillation. This creative force – “life,” in Dr. Still’s lexicon – exists outside of the material fascia, but directly influences it through “Potency,” which governs the behavior of charge. The engagement of material reality by the non-material force field of the Breath of Life begins with its manifestation of Potency. Potency resides in the zero-point field but manifests as a fluctuation of material fluid. It produces the fluctuation through moving charge, and water follows. These truths are available through PRT.

Dr. Still referred to spirit, from which Dr. Sutherland acquired his inspiration. Dr. Still said, “When matter ceases to be divisible, it then becomes a fluid of life.”[20] From this quotation, we realize that Dr. Still had a conception of the vacuum energy before physics had defined it. He also said, “Life enters the forest of flesh as man.”[21] From this, I interpret Dr. Still to say that combining life with flesh creates the human form. He conceived that biogen, tissue imbued with life, came from the parent causes of the celestial and terrestrial worlds. “Thus man’s body is a form given by celestial life to the terrestrial life.”[22] “…human life, in form and motion, is the result of conception by the terrestrial mother from the celestial father.”[23] I translate Dr. Still’s meaning to modern concepts of the zero-point field, the benefit of which he did not have.

These quotations lead us to the prospects of Rupert Sheldrake’s morphogenetic field.[24] He declares that all living things are expressions of pre-existing, unseen patterns in a field of energy. He confirmed his hypothesis of morphogenetic fields when he took a repeat image using Kirlian photography of a partially cut leaf that showed a persistent energy field of the whole leaf. An energy field of the whole leaf remained when part of the physical leaf did not.

What’s more, Alfred Pischinger, PhD,[25] an expert in the extracellular matrix agreed with anthroposophical physicians that the ECM is the morphological representation of the etheric body. Anthroposophical medicine, derived from the philosophy of Rudolph Steiner, includes the etheric body in their philosophy. The etheric body was the focus of Robert Fulford, DO, who often used mechanical means for osteopathic corrections (percussion hammer and HVLA) to obtain an etheric rebalancing. Of course, this fits with Dr Still’s declaration that the soul dwells in the fascia. We can extend his meaning of soul to the etheric body and the morphogenetic field.

As Osteopaths, we attend to the fascia, but our ultimate purpose is to utilize what nature does to create and maintain the form of the organism. It utilizes the etheric body, that blueprint from which the body is generated and maintained. Primary respiration in the fascia is the product of the interrelationships among the etheric body, the ECM, the Potency producing a fluctuation of extracellular fluid which transmits the Breath of Life and supplies the impetus for living activities such as metabolism. Potency uses charges in the tissue and water to move elements of fascia to their original structure. Osteopaths use hands-on intention to take advantage of these factors in osteopathic treatment. In healing, Intelligence or Memory, a characteristic of the Breath of Life partners with intention and attention of the operator to recreate original structure. The image of normal anatomy in the mind of the operator harmonizes with the Memory of the original function to recreate the original structure. Both the “Template” of the structure and “Memory” of the function are elements of the Breath of Life, according to PRT.

In treatment, osteopaths engage the form as it was becoming in its embryonic stage or rely on the fully formed pattern, but in either case, the orientation of the fibers of the fascia will align with the function from which it originated. The Template for the organism manifests as the structure that its function represents. The template unfolds as the extracellular matrix, the scaffolding from which organs, nerves and vessels emerge to carry out the original intent of function.

The channel theory of Traditional Chinese medicine provides the formula that Qi (Breath of Life) equals electricity plus intelligence that is delivered by fluid through fascial channels that we can manipulate. Osteopathy from Dr. Still and Dr. Sutherland says the same thing.

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[1] *Benias, Wells, Theise, Structure and distribution of an unrecognized interstitium in human tissue, Scientific Reports, 8, 4947 (2018).

[2] Stark, Still’s Fascia, Jolandos, 2007.

[3] Still, Philosophy of Osteopathy, 164.

[4] Still, Philosophy of Osteopathy, 165.

[5] Still, Philosophy of Osteopathy, 163.

[6] Lee, Interface: Mechanisms of Spirit in Osteopathy, Stillness Press, 2005.

[7] Lee, Living Matrix: A Model for the Primary Respiratory Mechanism, Explore, November/December 2008.

[8] Nordenstrom, Biologically Closed Electric Circuits, Nordic Medical Publications, 1983.

[9] Vern, Low-frequency oscillation of cortical oxidative metabolism in waking and sleep, J Cereb Blood Flow Met, 8:215-226, 1988.

[10] Olsen, Andersen, Lunding, Brasen and Poulson, Regulation of Glycolyitc Oscillations by Mitochondrial and Plasma Membrane H⁺-ATPases, Biophys J, 2009May6;96(9).

[11] Lee, Interface, Stillness Press, 2005.

[12] Ingber, Tensegrity: The architectural basis of cellular mechanotransduction, Annu Rev Physiol, 59:575-599, 1997.

[13] Lee, Interface, Stillness Press, 2005.

[14] Still, Philosophy of Osteopathy, 35.

[15] Becker, The Body Electric, William Morrow, 1985.

[16] Ibid.

[17] Oschman, Energy Medicine, Churchill Livingstone, 2000.

[18] Ibid.

[19] Lee, Primary Response Testing, a practical method of engaging the Intelligence of the Tide, taught in courses.

[20] Still, Philosophy and Mechanical Principles of Osteopathy, 254-5.

[21] Still, Philosophy and Mechanical Principles of Osteopathy, 258.

[22] Still, Philosophy and Mechanical Principles of Osteopathy, 255.

[23] Still, Philosophy and Mechanical Principles of Osteopathy, 251-2.

[24] Sheldrake, A New Science of Life, Tarcher, 1981.

[25] Pischinger, Matrix and Matrix Regulation, Heine, 1991.