What is The Extracellular Matrix?

The Extracellular Matrix (ECM) is a large network of proteins and other molecules that surround, support, and give structure to cells and tissues in the body. R

The ECM helps cells attach to/communicate with nearby cells.

It also plays an important role in cell growth, cell movement, and other cell functions. R

Imagine the ECM like a scaffolding for your the cells.

This scaffolding helps support and give structure, allowing the cells to climb, connect, and talk to each other, while allowing them to move around and grow properly.

The ECM is surrounded by what is called Interstitial Fluid, so sometimes these are used interchangeably, but they mean different things.

There are two parts of the ECM: R

the interstitial matrix, which forms a three-dimensional porous network surrounding the cells (especially connective tissues)
the pericellular matrix, which is more compact and forms a layer adjacent to the cells

Cell Walls and The Extracellular Matrix

Cell walls are made of a phospholipid bilayer membranes, which allow for certain molecules to pass through or be repelled. R

Normal Wound Healing Cycle

As we discussed in the Wound Healing post, people can get stuck in chronic wound healing, rather than finishing the entire wound healing cycle.

Normally, wounds heal in stages: stop bleeding, fight infection, rebuild tissue, and close the opening.

More specifically:

Normally when you have an injury, first step is to come in and stop the bleeding (hemostasis) and fight invading pathogens (inflammation).
After that there is a temporary scar created to close the gap from the injury as cells grow (proliferation) and then over the next month to a year the structure is remodeled to create healthy new collagen (remodeling).

Chronic Wound Healing Cycles

When this process gets stuck, injuries do not heal correctly.

Chronic wounds get stuck as something disrupts this healing process…

Why Don't Chronic Wounds Heal?

Constant inflammation (TLR agonism, endotoxin looping and metabolic endotoxemia, bioaccumulation, etc)
Infection
Dead tissue
Leaky junctions

What Goes Wrong During Healing Stages?

You’re not stopping bleeding correctly, so clots might be too strong or not breaking down properly, causing delays moving through the cycle.

You’re not clearing the pathogen (like persistence), so chemical messengers (cytokines) get imbalanced, creating cytokine storms (aka “herxing” and “flares”).

You do not have the cofactors to rebuild tissue (put those fibroblasts & keratinocytes to work!) and close up the wound, but your tissue rebuilders move too slowly.

Anyway, this results in a slow, frustrating healing process that can lead to problems like easily acquiring more infections, deeper tissue damage, and poor collagen formation (you have a connective tissue disorder all of a sudden).

Endotoxin Tolerance and the ECM

Being stuck in Endotoxin Tolerance (chronic M2 macrophage state) contributes to ECM stiffness. R

Hacks to Remodel the Extracellular Matrix

Rebuilding the ECM takes months to years.

Acetylcholine

Rebuilding the extracellular matrix requires a lot of phospholipids, which may get concerted into Acetylcholine (ACh).

This is good for people with vagus nerve issues as it can be calming by activating the parasympathetic side.

Cholinegrics come with a double edge sword, as if you are exposed to a lot of Acetylcholinesterase inhibitors (AChEis) such as pesticides, ACh can make you feel depressed and brain foggy.

If you have poor reactions to cholinergics, eat clean/organic, take Carboxy, and work on your acetylcholineesterase levels.

Strategies

I prefer to combine strategies for a compounding beneficial effect.

Acupuncture (via acting as a remodeling inducer via hormesis and nrf2 as well)
Body Bio PCs (phosphatidylcholine and phosphatidylserine)
Collagen (and other GAGs like Glucosamine Sulfate, Chondroitin Sulfate, and Hyaluronic Acid)
Exercise (stimulates growth factor release of the ECM) R
Lecithin (similar to PCs) R
Liposomes (like Membrane Mend) as they are made of phospholipids
Plasmalogens (sometimes found in unoxidized Fish Oils)
SPMs (a byproduct of Fish Oils after interacting with the body)

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What is The Extracellular Matrix?