Extracellular Matrix Definition

The extracellular matrix can be thought of as a suspension of macromolecules that supports everything from local tissue growth to the maintenance of an entire organ. These molecules are all secretions made by neighboring cells. Upon being secreted, the proteins will undergo scaffolding. Scaffolding, in turn, is a term used to describe the ephemeral structures that form between individual proteins to make more elaborate protein polymers. These rigid, albeit temporary protein structures will lend the matrix a viscous consistency. One can think of the extracellular matrix as essentially a cellular soup, or gel mixture of water, polysaccharides (or linked sugars), and fibrous protein. This leads us to another category of molecule found within the extracellular matrix called the proteoglycan. The proteoglycan is a hybrid cross of a protein and a sugar, with a protein core and several long chain sugar groups surrounding it. All of the molecular groups that make up these macromolecules will lend them special properties that will dictate the kind of hydrophobic or hydrophilic interactions they can participate in.

Much like the ephemeral interactions they form in this aqueous solution, the actual structures of the proteins themselves are notably dynamic. The molecular components found within their structures are always changing. The remodeling they undergo is certainly aided by protease enzymes found in the matrix and can be modified by post-translational changes. The extracellular matrix has a functional value in buffering the effects of local stressors in the area. But we will discuss many more of the functions the matrix serves in detail below.

Extracellular Matrix Function

Living tissue can be thought of as a dynamic meshwork of cells and liquid. Despite their close proximity to each other, the cells of a tissue are not simply tightly wound together. Instead, they are spaced out with the help of the extracellular meshwork. The matrix will act as a kind of filler that lies between the otherwise tightly packed cells in a tissue. Furthermore, not only is the matrix filling the gaps in between these cells but it is also retaining a level of water and homeostatic balance. Perhaps the most important role of the extracellular matrix, however, can be distilled down to the level of support it provides for each organ and tissue.

The extracellular matrix directs the morphology of a tissue by interacting with cell-surface receptors and by binding to the surrounding growth factors that then incite signaling pathways. In fact, the extracellular matrix actually stores some cellular growth factors, which are then released locally based on the physiological needs of the local tissue. On the other hand, a tissue’s morphology is another way to describe the “look” or appearance of the organ or tissue. The physical presence of proteins and sugars in the matrix also have the benefit of cushioning any forces that may be placed upon the surrounding area. This prevents the cellular structures from collapsing or the delicate cells from going into shock. Since the extracellular matrix is thick and mineralized despite its water rich content, it has the additional function of keeping the cells in a tissue separate and physically distinct.

More direct applications of the extracellular matrix include its role in supporting growth and wound healing. For instance, bone growth relies on the extracellular matrix since it contains the minerals needed to harden the bone tissue. Bone tissue will need to become opaque and inflexible. The extracellular matrix will allow this by letting these growth processes take ample opportunity to recruit extracellular proteins and minerals to build and fortify the growing skeleton. Likewise, forming scar tissue after an injury will benefit from the extracellular matrix and its rich meshwork of water insoluble proteins.

Extracellular Matrix Components

The extracellular matrix is mostly made up of a few key ingredients: water, fibrous proteins, and proteoglycans. The main fibrous proteins that build the extracellular matrix are collagens, elastins, and laminins. These are all relatively sturdy protein macromolecules. Their sturdiness lends the extracellular matrix its buffering and force-resisting properties that can withstand environmental pressures without collapsing. Collagen is actually a main structural component of not only the matrix, but also of multicellular animals. Collagen is the most abundant fibrous protein made by fibroblasts, making up roughly one third of the total protein mass in animals. In the matrix, collagen will give the cell tensile strength and facilitate cell-to-cell adhesion and migration. Elastin is another fiber that will lend tissues an ability to recoil and stretch without breaking. In fact, it is because elastin and collagen bind and physically crosslink that this stretching is limited to a certain degree by collagen. Fibronectin is first secreted by fibroblast cells in water soluble form, but this quickly changes once they assemble into an un-dissolvable meshwork. Fibronectin regulates division and specialization in many tissue types, but it also has a special embryonic role worth mentioning where it will aid in the positioning of cells within the matrix. Laminin is a particularly important protein. It is particularly good at assembling itself into sheet-like protein networks that will essentially be the ‘glue’ that associates dissimilar tissue types. It will be present at the junctions where connective tissue meet muscle, nerve, or epithelial lining tissue.

Collagen triple helix
The image depicts a computerized illustration of the three-dimensional structure of collagen protein

Roles of fibrous protein:

  • Collagen – stretch resistance and tensile strength (i.e. scar formation during wound healing)
  • Elastin – stretch and resilience
  • Fibronectin – cell migration and positioning within the ECM, and cell division and specialization in various tissues
  • Laminin – sheet-like networks that will ‘glue’ together dissimilar types of tissue

On the contrary to fibrous proteins that resist against stretching, proteoglycans will resist against compression. This refers to the forces pushing down on the tissue that would otherwise “squash” or collapse it. This ability stems from the glycosaminoglycan group in the proteoglycan. Glycosaminoglycan, or GAGs, are chains of sugar that will vary and thus lend the molecules different chemical properties. Moreover, GAGs are the most highly negatively charged molecule animal cells produce. This charge will attract GAGs to positively charged sodium ions. In living tissue, water follows the movement of sodium. This will bring us to a situation where water and GAGs will attract as well, which will lend water within the extracellular matrix a characteristic resistance to compression.

Quiz

1. Which of the following is not a fibrous protein type mentioned?
A. Elastin
B. Proteoglycan
C. Collagen
D. Laminin

Answer to Question #1
B is correct. Proteoglycans are a molecular group separate from fibrous proteins with different characteristics. Proteoglycans will notably have a protein core with surrounding sugar groups, and unlike fibrous protein will not lend cell characteristic stretch-resistance.

2. Identify the distinction between fibrous protein and proteoglycans, per the article:
A. Fibrous protein is more capable of handling aqueous environments
B. Proteoglycans serve more of a filler role in the spaces between the cells in a tissue
C. Fibrous proteins resist against compressive forces
D. Proteoglycans resist against compressive forces

Answer to Question #2
D is correct. Unlike fibrous proteins, which will resist against stretching with the structures they form that actually lend the tissue tensile strength and rigidity, proteoglycans will resist against “squashing” or compressive forces.

References

  • Franz et al (2010). “The extracellular matrix at a glance.” J Cell Sci. 123(24): 4195-4200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995612/
  • Alberts, B et al (2002). “The Extracellular Matrix of Animals.” Molecular Biology of the Cell: 4th edition. https://www.ncbi.nlm.nih.gov/books/NBK26810/
  • Study (2017). “Extracellular Matrix.” Study.com. Retrieved on 2017-08-15 from http://study.com/academy/lesson/extracellular-matrix-function-components-definition.html