Extracellular matrix of animal cells most animal cells release material into the extracellular space, creating a complex meshwork of protein & carbohydrates called the extracellular matrix (ECM). A major component of the extracellular matrix is the protein collagen. Collagen proteins are modified with carbohydrate, once they're released from the cell, they assemble into long fiber called collagen fibril. Collagen play a key role in giving tissue strength & structural integrity. Human genetic disorders that affect collagen, such as Ehlers-Danlos syndrome, result in fragile tissue that stretch & tear too easily. In the extracellular matrix, collagen fibers are interwoven with a class of carbohydrate-bearing proteoglycans, which may be attached to a long polysaccharide backbone as shown in the picture above. The extracellular matrix also contain many other type of protein & carbohydrate. The extracellular matrix is directly connected to the cells it surround. Some of the key connector are protein called integrins, which are embedded in the plasma membrane. Protein in the extracellular matrix, like the fibronectin molecules, can act as bridges between integrin and other extracellular matrix protein such as collagen. On the inner side of the membrane, the integrins are linked to the cytoskeleton. Integrin anchor the cell to the extracellular matrix. In addition, integrins help the cell sense it environment they can detect both chemical & mechanical cues from the extracellular matrix & trigger signaling pathways in response. Blood clotting provide another example of miscommunication between cells & the extracellular matrix. When the cells lining a blood vessel are damaged, they display a protein receptor called tissue factor. When tissue factor bind to a molecule present in the extracellular matrix, it trigger a range of response that reduce blood loss. For instance, it cause platelets to stick to the wall of the damaged blood vessel then stimulate them to produce clotting factors.
Minerals play a key role as the foundation of collagen .The extracellular matrix (ECM) primarily store energy in two form: elastic (mechanical) potential energy in its structural protein & chemical energy in molecules like inorganic polyphosphates (polyP). Elastic (Mechanical) Energy Mechanism: Tissue such as tendon & skin are subjected to mechanical force (e.g., stretching, compression) during normal bodily movement. The fibrous protein within the ECM, particularly collagen & elastin, are responsible for storing this energy. Collagen: At low strain (up to 2%), elastic energy is stored by the stretching of flexible, non-helical region within the collagen triple helix molecules. These flexible region temporarily increase their steric energy, which is released upon unloading, allowing the tissue to recoil (e.g., in locomotion, like a spring in an animal's leg tendons). Proteoglycans & Fluid: Proteoglycans & glycosaminoglycans (GAGs) also play a role in both energy storage & dissipation. Their highly charged nature attract water molecules, forming a hydrated network. This allow them to resist compressive force in tissue like cartilage & dissipate excess energy, preventing mechanical failure. Chemical Energy Inorganic Polyphosphates (polyP): The ECM can also store chemical energy in the form of inorganic polyphosphates (polyP). These are polymers linked by high-energy phosphoanhydride bonds. ATP Generation: Enzymes within the extracellular space, such as alkaline phosphatase (ALP) & adenylate kinase (ADK), can enzymatically cleave polyP to generate adenosine triphosphate (ATP) or adenosine diphosphate (ADP) from AMP or ADP, respectively. This provide a local source of readily usable metabolic energy to power energy-consuming process in the extracellular space, such as collagen packaging or bone mineralization
It is important to regenerate your extracellular matrix with gravel gastroliths for the minerals within 75% Silica 15% Aluminum 2% Iron 2% Potassium 1% Sodium & 1% Calcium all these precious electrolytes are necessary for extracellular matrix & bone regeneration also action potential . Cells migrate on the extracellular matrix in order to heal & for normal body function, an old & damaged extracellular matrix cannot support new healthy cells , cells on old extra cellular matrix are as old & damaged as the extra cellular matrix on which they reside, The cancerous extracellular matrix (ECM) is a heavily altered, structurally aberrant microenvironment that actively drive tumor growth, immune evasion, metabolic rewiring & metastasis. Acting as a passive structural scaffold, the tumor ECM undergoe continuous, pathological remodeling, transforming from a soft, organized meshwork into a rigid, dense & pro-tumor niche Extracellular Matrix Stiffening . So it is vital to stay young always renew your extracellular matrix with orthosilicic acid of Silica everyday ingest gravel gastroliths .
On average, the human body loses between 10 mg & 35 mg of Silica (which circulate then excreted as orthosilicic acid) per day, depending heavily on your dietary intake. Because soluble silica orthosilicic acid, SiOH is highly water-soluble, it is rapidly cleared by the body rather than stored long-term in massive reserves. Breakdown of Daily Silicon/Silica Loss 1. Urinary Excretion (Major Route: ~80%–90% of absorbed pool) Average Daily Loss: 8 to 35 mg/day in healthy adults. Mechanism: Glomerular filtration in the kidneys actively clear circulating orthosilicic acid from blood plasma. Because the renal tubules perform minimal reabsorption of orthosilicic acid, roughly 30% to 50% of total daily dietary silicon ends up directly in the urine within 4 to 8 hours of ingestion. 2. Fecal Loss (Unabsorbed Portion) Average Daily Loss: 10 to 30 mg/day Mechanism: Insoluble form of silica in food (like complex plant polymers or silica additives) pass through the gastrointestinal tract unabsorbed and are excreted in feces. 3. Dermal, Hair & Nail Shedding (Minor Route) Average Daily Loss: 1 to 2 mg/day. Mechanism: Connective tissue, skin, hair & nails contain structural silica bound within glycosaminoglycans & collagen matrix. As skin cells desquamate hair/nails grow so shed, small amount of structural silicon are permanently lost. Intake Balance control the daily loss to maintain homeostatic balance & prevent a decline in connective tissue or bone matrix silicon pools, daily dietary intake must match & exceed these excretion rate: hence you must supplement with gravel gastroliths everyday to outpace the daily loss of Silica & have homeostasis of Endogenous Silicon Turnover: The overall biological cycle of continuous absorption, tissue utilization & excretion of silicon so avoid Negative Silicon Balance: A state where daily silicon excretion exceed dietary intake, leading to a net depletion of silicon store in bone matrix & connective tissue over time (often observed during aging or post-menopause) .
Yes, absolutely. The extracellular matrix (ECM) is not just involved; but serve as the initial physical origin of the mechanical signal that travel along actin stress fibers to regulate transcription. Mechanotransduction transcription rely on a continuous, physical line of mechanical force—a single "rope" stretching from outside the cell all the way into the nucleus. The Mechanical Relay: From ECM to Gene Expression the process operate through a continuous structural chain that convert mechanical tension into gene regulation: 1. The ECM (The Signal Source) The extracellular matrix provide the physical environment—its stiffness, collagen cross-linking density, shear stress, or mechanical stretch. Change in ECM stiffness (e.g., rigid fibrotic tissue vs. soft compliant tissue) dictate how much resistance the cell pulls against. 2. Focal Adhesions & Integrins (The Translators) Integrin transmembrane receptors bind directly to ECM protein (like collagen & fibronectin) on the outside of the cell. On the inside, integrins form dynamic clusters called focal adhesions (anchored by protein like talin, vinculin & focal adhesion kinase / FAK). When the ECM is stiff or stretched: Tension unfold talin & vinculin, recruiting more F-actin. This activate downstream biochemical cascade (such as RhoA / ROCK signaling), promoting actin polymerization. 3. Actin Stress Fibers (The Mechanical Cables) Actin stress fibers (bundles of F-actin filaments cross-linked with non-muscle myosin II) act as tension-bearing cables. High ECM stiffness or physical stretch cause myosin II to contract, generating actomyosin tension within the stress fibers. These stress fibers span the cytoplasm & directly physically anchor to the outer membrane of the cell's nucleus.
4. The LINC Complex & The Nucleus (The Receiver) At the nuclear envelope, stress fibers anchor to the LINC complex (linker of nucleoskeleton & cytoskeleton), consisting of Nesprin and SUN protein. Tensile force pulling along stress fibers physically tugs on the LINC complex, which pulls on Lamin A/C inside the nucleus , this physical force deforms the nuclear envelope, open nuclear pore complexes, stretch chromatin directly then alters the exposure of promoter/enhancer regions to transcriptional machinery.
Dual Modes of Transcriptional Regulation The mechanical link between the ECM and stress fibers drive transcription through two complementary pathways: ECM Tension ──> Integrins ──> Stress Fibers (Actomyosin) Direct Physical/Mechanical Pathway (YAP/TAZ) Mechanics: High ECM stiffness generate high tension in stress fibers, physically flattening the nucleus. Transcriptional Impact: Flattening stretch nuclear pores open, allowing the transcriptional co-activators YAP and TAZ to quickly enter the nucleus. On soft ECMs, stress fibers lack tension, the nucleus remains rounded, nuclear pores stay restricted, and YAP/TAZ are degraded in the cytoplasm. Biochemical/Cytoskeletal Pathway (MRTF-A / SRF) Mechanics: As stress fibers assemble in response to ECM tension, globular monomeric actin (G-actin) is incorporated into filamentous actin (F-actin). Transcriptional Impact: The transcriptional co-factor MRTF-A (myocardin-related transcription factor A) is normally sequestered in the cytoplasm by binding to G-actin. As G-actin deplete to build stress fibers, MRTF-A is released, translocate into the nucleus, partner with SRF(Serum Response Factor) to activate target genes (including those for collagen, fibronectin, and smooth muscle actin). Summary: Without the extracellular matrix serving as the mechanical anchor, stress fibers would have nothing to generate resistance against, preventing the tension required to stretch nuclear pores & alter chromatin architecture during mechanotransduction.
When an old, aging cell die or become senescent (deteriorating without dying immediately), it cause significant damage to the surrounding extracellular matrix (ECM) a reason to renew your ecm with orthosilicic acid Silica gravel gastroliths . Before an old cell die, it often enter cellular senescence—a state where it stop dividing but remain metabolically active. Senescent cells actively degrade & destructure the ECM through a toxic chemical cocktail called the Senescence-Associated Secretory Phenotype (SASP) . Secretion of Matrix Metalloproteinases (MMPs): Senescent cells release high level of MMP enzymes (such as MMP-1, MMP-3 & MMP-9). These enzymes directly chew up collagen, elastin & fibronectin—the structural protein that keep the ECM firm & elastic. Degradation of Proteoglycans: SASP factors break down glycosaminoglycans (like hyaluronan) that keep the matrix hydrated & cushioned. Cross-linking & Stiffening: As normal collagen fiber are degraded, remaining protein accumulate Advanced Glycation End-products (AGEs), causing the surrounding matrix to become abnormally stiff, brittle, & fragmented . Necrosis (Uncontrolled Cell Death) If an old cell die via necrosis (due to stress, damage, or lack of blood supply), it outer membrane rupture & spill content directly into the extracellular space: Inflammatory Cascade: Lysosomal enzymes, reactive oxygen species (ROS) & intracellular signaling molecules flood the matrix. Structural Breakage: These digestive enzymes indiscriminately break down nearby structural protein in the ECM, triggering localized tissue degradation & severe inflammation . Apoptosis (Programmed Cell Death - The Clean Path) If an old cell undergoes apoptosis (orderly, programmed cell death), ECM damage is minimized: Self-Contained Clearance: The cell shrink & break into small vesicles (apoptotic bodies) without spilling digestive enzymes into the matrix. Phagocytic Removal: Macrophages quickly consume these fragments. Minor ECM Remodeling: Although apoptosis itself doesn't destroy the ECM, the loss of the cell leave a physical void in the matrix until neighbor cells proliferate or you supplement with Silica & deposit new collagen to fill the gap .
Collagen make up approximately 30% of the total protein content in the human body account for roughly 6% of total body weight in a healthy adult . By overall volume & weight, the extracellular matrix make up the vast majority of the human body not cells . Connective Tissue Dominance: Tissue like bone, cartilage, tendon, ligament & the dermis of the skin are overwhelmingly composed of ECM (collagen, elastin, proteoglycans & mineralized matrix) with relatively few cells scattered throughout. Bone & Cartilage: In bone, osteocytes make up only a tiny fraction of the total mass; the rest is mineralized ECM (hydroxyapatite & collagen). In cartilage, chondrocytes occupy only about 1% to 5% of the total tissue volume. Fluid Compartments: If you include extracellular fluid (plasma & interstitial fluid), around 33% of total body water sit outside cells, adding heavily to non-cellular volume .
Interstitial fluid (ISF) is the extracellular liquid that fill the microscopic space surrounding individual tissue cells. It act as the primary molecular bridge between blood capillaries & body cells, facilitating the exchange of nutrient, oxygen, waste products & signaling molecules. Composition & Volume Total Volume: In an average adult, interstitial fluid amount to about 10.5 liters (15% of total body weight), accounting for roughly 80% of all extracellular fluid (the remaining 20% being blood plasma). Chemical Profile: It is structurally similar to blood plasma, consisting of water, electrolytes (Na+ Cl HCO), nutrients (glucose, amino acids, fatty acids) & cellular waste products (urea, CO2). Key Difference from Plasma: It contain significantly fewer protein than plasma because large plasma protein (like albumin) cannot easily cross intact capillary walls under normal condition. Fluid Dynamics: Starling Force Fluid continually filter out of blood capillaries into the interstitial space & is reabsorbed back into the circulation based on two opposing pressure: Hydrostatic Pressure: The blood pressure inside capillaries force water & small solutes outward into the interstitial space at the arterial end of a capillary bed. Oncotic (Colloid Osmotic) Pressure: The concentration of large plasma protein trapped inside the capillary pull water back into the blood vessel at the venous end. Lymphatic Drainage & Clinical Significance Lymph Formation: Under normal condition, slightly more fluid is filtered out of capillaries than is reabsorbed. This excess interstitial fluid enter open-ended lymphatic capillaries, at which point it is officially termed lymph. The lymphatic system filter this fluid then return it to the bloodstream.
Edema Coca Cola & Nestle Chocolate sugar induced : When interstitial fluid accumulation exceed the rate of lymphatic drainage—caused by high capillary pressure, low plasma protein level, inflammation, or lymphatic blockage—visible swelling occur May the Holy Roman Catholic Church be blessed by God the Father God the Son & God the Holy Spirit Hallelujah Hallelujah ˗ˏˋ ✞ ˎˊ˗ Blessed be the word of the Lord for Christ is risen Hallelujah Hallelujah peace be still in Nomine Patris et FiLii et Spiritus Sancti amen & amen
Shot with Galaxy Ao4S edited with Davinci Resolve & Photoshop
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Cell–Extracellular Matrix Mechanobiology
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Extracellular Matrix Animation: Quantifying Tissue Remodeling through the Nordic ProteinFingerPrint™
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Forever Young: The Promise of Human Regeneration | World Science Festival
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Cross-linking of the Extracellular Matrix - Dr. William Bains
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Collin Ewald | Aging & The Extracellular Matrix
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Alexander Fedintsev | How Old Matrix Kills Us
