The Extracellular Matrix: The Fascinating Part of the Human Body You’ve (Probably) Never been Told About.

You won’t look at a human or animal body the same way after learning this.

If you’d asked me just a week ago what you’d be left with if you could magically make all the human cells and their contents (living and dead, whole or fragmented) in the human body disappear, I (and I suspect I am fairly typical) would have answered that you’d be left with the bones (without the marrow), the teeth (with the fillings but not the pulp), the blood plasma, the lymph, the cerebrospinal fluid, the urine in the bladder and the kidneys, the water in the stomach and intestines, the food and that part of the feces not made up of human cells sloughed off of the inner surface of the digestive tract in the digestive tract, bacteria, viruses and parasites, the oil on the hair and skin, the mucus in the respiratory, digestive, and reproductive tracts, the tears in the tear ducts, the fluid in the thoracic cavity, if any, the air in the lungs and gut and thoracic cavity. The synovial fluid.

I would have figured that the cartilage, ligaments, and tendons would disappear because they are made of cells called chondrocytes.

I would have been unsure about hair and nails, but apart from that I would have been feeling confident, and pleased with myself.

And yet I had overlooked a huge part of the body that I had never heard of: the extracellular matrix. I had imagined that the tissues, organs, and the whole body was a bone skeleton with cells attached to the bones and to each other. I imagined the cells to be joined directly to each other like atoms in a crystal.

In fact, the cells are not really touching, on the whole, let alone firmly joined to each other. Rather the cells sit in a solid matrix of a mixture of proteins, especially collagen, which is like a plastic or hardened glue or rubber. The matrix is secreted by the cells, and holds them in place and connects them to each other. In bone, the extracellular matrix is strong, rigid and hard, while in cartilage it is like strong but flexible like some types of rubber or plastic. In the brain it is very soft and flexible. The differences in rigidity, strength and hardness come from different mixes and densities of proteins, except in the case of bone which has a lot of calcium compounds (minerals) in the extracellular matrix.

Some analogies: concrete is bits of gravel in a cement matrix; frozen blood is frozen blood cells in a matrix of frozen blood plasma; a current bun is currents in a bread matrix; a chocolate chip cookie is chocolate chips in a matrix of cookie; an almond chocolate bar is almonds in a matrix of chocolate; small pieces of fruit in a matrix of jelly.

The current bun may be the best image for a tissue like liver, kidney, or muscle, because the extracellular matrix is usually somewhat elastic. A chocolate chip cookie is like bone. Jelly with pieces of fruit in it is like the brain.

Perhaps I should say “extracellular matrices” as seemingly each tissue has its own extracellular matrix. It doesn’t matter. The point is that if you removed all the human cells from a human body you would be left with a lot more than than I and most people would have imagined. In fact, you’d be left with an entire body, though it would be white to translucent, and it would weigh a bit less, and be a bit softer in places. All of the skeleton and teeth and cartilage would be almost unchanged, while the skin, muscle, and other tissues would be somewhat paler, whiter, and more translucent, (a bit like a ghost) but the person would would still be recognizable, if when alive he or she was fairly slim. The biggest difference would be the disappearance of hair and nails, and fat tissue. The fat is inside the cells, you see. The phrase a shadow of one’s former self, comes to mind.

If you dissected the body, you’d find every organ in position, white to translucent. Amazing to think about it.

That’s because every tissue in the body has its own extracellular matrix. So what is it? The extracellular matrix is the complex mass built up from the secretions of the cells in it. It acts as a framework that holds the cells in place, so that the cells do not have to be attached directly to each other. Thus it functions a bit like a soft skeleton. Not only that, but, like the blood and lymph, it signals to cells with chemicals it contains. The cells modify the extracellular matrix and vice versa.

This is not a matter of speculation. In recent years great progress has been made in decellularization, which is where the cells of an organ like the brain, or small intestine, or heart are killed and dissolved and washed away using special enzymes and/or detergents that leave the extracellular matrix largely unharmed. The reason this is a hot area of research is that the extracellular matrix can be used as a scaffold for new cells and thus a new organ can to some extent (they are still working on it) be created ready for implantation into a patient.

When a part of the body is soft, like the brain, that’s because the extracellular matrix of the brain is soft. When it’s hard, like bone, that’s because the extracellular matrix of bone is hard.

Extracellular matrix, which is made up of an organic matrix (30%) containing proteoglycans (but less than cartilage), glycosaminoglycans, glycoproteins, osteonectin (anchors bone mineral to collagen) and osteocalcin (calcium binding protein). There are collagen fibres (mostly type I (90%), with some type V). Only 25% of bone is water. Almost 70% of bone is made up of bone mineral called hydroxyapatite. (source: https://www.histology.leeds.ac.uk/bone/bone.php)

Before the extracellular matrix is calcified, the tissue is called osteoid (bone-like) tissue. When the concentrations of calcium and phosphate ions rise high enough, they are deposited into the extracellular matrix, and the bone calcifies.

When it’s elastic, like skin, it’s because the extracellular matrix of skin is elastic. As you get old, your skin gets less elastic, and that’s because the extracellular matrix of your skin gets less elastic. Do you what I’m getting at here? When you grab someone, you are grabbing their extracellular matrix. When you hit someone, you are hitting their extracellular matrix.

When you get hold of someone’s fat with your hand, you are getting hold of the extracellular matrix of the skin, and the extracellular matrix of the adipose tissue that contains the fat, under the skin. The fat is inside the cells, and so this is a rare case where you are feeling the cells of another person in conjunction with the extracellular matrix and not just the extracellular matrix.

Adipose (fat) tissue is a loose connective tissue composed primarily of lipid-filled cells known as adipocytes (fat cells) together with smaller numbers of fibroblasts and immune cells embedded in an extensive, collagenous extracellular matrix penetrated by a network of blood vessels (1).

Remember that extracellular matrix is not alive. So a lot more of the body is nonliving than we tend to think. It’s not just (the noncellular parts of) bones, and teeth that aren’t alive, it’s the entire framework of the flesh, that which makes our flesh stay in one piece rather than scatter like dust (individual cells). Most of what we see (all except the color) and nearly all of what we feel. What we see and feel is mainly the extracellular matrix which is nonliving. The living parts of the body are dotted around this framework.

We are, physically, mostly nonliving matter (this goes for animals, too). So we are more like trees than we thought.

Our bodies are not of cells, but rather contain cells. The cells create and manage and animate the rest of the body. Thus each cell is doing more than we thought. The cells are dotted around the body, like motors, computers, and chemical reactors (muscle, nerve cells, and liver cells, for example) making it do all the things it does.

Another possible image is that of a sailing ship with a crew. The crew are the cells, and the ship is the extracellular matrix. But this ship is continuously being built by the crew, not just maintained and controlled. Very different from a ship made of people.

What Unsplash returned when searched for “extracellular matrix”.