Extracellular Matrix Animation

The human body is formed from a single cell that divides into trillions of cells which make up the unique organs of our bodies. All cells in the human body carry the same genetic material. The only way they know how to interact, behave and form the organs is because of the context that surrounds them. This context is called the extracellular matrix. The extracellular matrix is a dynamic 3 dimensional network that provides stability, signalling and structural support to the organs.

The main type of proteins in the extracellular matrix is collagens. Several different types of collagen exist. One example is type 1 collagen that creates fibres and provides strength and support to the organs. Another example is type 4 collagen that is found below the cells.

Type 4 collagen forms a structure that helps maintain the barrier between tissue compartments and works as the first line of defence. It interacts with other proteins and thereby enables signalling to the cells. The collagens are different in all organs of the human body. This means that the collagens of the heart are different from the collagens of the liver and lungs. In the lungs for example, the alveoli membrane is mainly composed of type 4 collagen, which helps the exchange of oxygen into the blood.

During development of chronic diseases such as lung fibrosis, the collagens and the interstitial matrix expand, the tissue becomes stiff, leading to a decreased lung function that can be life threatening for the patient.

The change in the collagens is seen not only in lung diseases, but in most chronic diseases such as cancer and cardiovascular diseases. The common denominator of all chronic diseases is severe tissue damage resulting in cell death and changes in collagen composition. Inflammatory cells migrate to the site of damage, secrete proteases, and consequently break down the collagen fibres, releasing collagen fragments Into the environment.

Fibroblasts are then activated to build large, complex collagen fibres. To form the fibres the fibroblasts secrete collagen proteins during this process and fragments are caved off to enable attachment of the collagen proteins to each other. Just like building blocks, the proteins come together to produce the strong fibres. The cleaved off fragments are then released into the environment where they attract more inflammatory cells. This maintains the vicious circle of build-up and breakdown of collagens that fuel the chronic diseases.

Both the build-up and breakdown collagen fragments are released into the blood where they circulate together with blood cells and can be used as targets for blood based biomarkers.