Whether it is a small earthworm or the largest animal, blue whale, they are all complex organisms composed of various cells that are glued by special adhesives into an orderly tissue to perform biological functions. Otherwise, multicellular animals would be a pile of sludge. So how are they stuck together, and what is the adhesive between them?
Component in animal extracellular matrix (ECM)
Animal ECM is a complex network that is attached by cell in all the tissues. The "adhesive" is various proteins or proteoglycans that are synthesized and secreted to extracellular environment via vesicles in fibroblasts.
① Proteoglycan is made up of glycosaminoglycan and peptide. Its 95% is carbohydrate that contains amino groups, and the remaining is peptide. Carbohydrates are linked to linear peptide covalently. Since they carry negative charges, water molecules are attracted by them to form a watery hydrogel. Therefore, animal tissue feels soft and is able to resist compression.
② The most abundant fibrous proteins in animal is collagen and elastin. Triple helix and many hydrogen bonds result in the high tensile strength in collagen. Like rubber bands, elastin makes tissues elastic. The very short hydrophilic regions are at both ends of peptide, and in the middle is a very large coiled hydrophobic region. When tension is applied, elastin stretches several times in length. The areas that contract and extend frequently have a lot of elastin, such as heart, skin, blood vessels and lungs.
③ The mesh like structure formed by collagen are not connected to cell directly. They bind to the receptors via adhesion proteins. Since most receptors are transmembrane integrated proteins that connect to intracellular microfilaments and intermediate filaments, ECM and cytoskeleton are essentially a unified structure.
Functions of animal extracellular matrix
The primary task is to provide physical support and mechanical strength. Cell behaviors such as survival, proliferation, development, and migration are all controlled by it.
Basement membrane provides physical support and filtration
Sometimes substances in ECM organize into a more orderly form, the basement membrane. In the skin, they act like a double-sided tape that connects the epidermis and dermis tightly. Other tissues wrapped by basement membrane are muscles and fat. Becoming a selective barrier to control material exchange is another function. In the kidneys, metabolic waste in the blood is filtered by basement membrane, and nutrients such as proteins, glucose, and inorganic salts are retained in the blood.
Metabolism regulation
Cells sense the stiffness and elasticity in their surrounding environment via ECM. These mechanical signals are converted into biochemical substance to alter metabolism. When they attach to a harder substrate, more energy is used by mitochondria, while on a softer substrate, they consume less energy. If ECM is hydrolyzed by enzymes, the synthesis and secretion of cartilage cells are reduced significantly.
In damaged tissues, fibroblasts remodel the ECM rapidly where other cells are recruited and attached. Growth factors are captured and stored in ECM to regulate local cells behavior for repair and regeneration. Cell division is promoted and apoptosis is inhibited. Immune cells gather at the wound site where the microbial invasion is prevented and the damaged matrix is eliminated. Therefore, it is crucial to construct an artificial extracellular environment for wound growth in tissue engineering and regenerative medicine. Natural connective tissue is often temporarily replaced by porous gelatin and hydroxyapatite that is consumed within six months, and the true ECM is left behind.
It is also related to cancer spreading closely. They can’t properly adhere to neighboring cells or ECM due to the mutations in adhesion protein. Additionally, enzymes are secreted to degrade ECM. Hence, cancer cells can easily escape away from primary site, invade surrounding tissues, and spread to distant sites. This is both a challenge and opportunity. The developing drugs that inhibit these degrading enzymes may be one of the prospects for defeating cancer.