Extracellular Matrix

Most cells synthesize compounds and materials destined to be secreted in the outside space of the cell (extracellular space). These materials form an extracellular matrix (ECM) that surrounds the cell and serves functions related to structure and communication with the extracellular environment.

The name extracellular matrix mainly refers to the components found outside of animal cells. However, fungi, plant cells, and some protists have an extracellular structure called the cell wall that some biologists consider a specialized extracellular matrix. Other sections discuss plant cell walls in more detail; therefore, we focus on animal cells’ extracellular matrix here.

The ECM is a network mainly composed of water and diverse proteins and carbohydrates; the abundance of each component depends on the type of tissue they are part of (figure 1). Some tissues are mainly formed by lots of cells with some ECM in between (like in the brain and cardiac muscle), and others, called connective tissues, are primarily ECM with scattered cells suspended within it.

The glycoprotein elastin is also common in ECMs and associates with collagen. Elastin forms elastic fibers that can extend, giving flexibility to tissues subjected to repeated stretch. Several tissues that have high amounts of elastin include vasculature (circulatory system) and lung tissues.

The ECM is connected to the outside of the cell membrane by other types of receptor glycoproteins, like fibronectins. The fibronectins bind to proteins called integrins that are embedded into the plasma membrane. The integrins span the whole plasma membrane width, and their cytoplasmic side binds with proteins attached to microfilaments (elements of the cell cytoskeleton). Therefore, these glycoproteins enable cell adhesion to the ECM.

The ECM provides mechanical support to the cells in a tissue and regulates intercellular adhesion and communication. Recent research shows that the ECM is highly dynamic and of vital importance. It determines and controls essential behaviors and characteristics of cells such as proliferation, adhesion, migration, polarity, differentiation, and apoptosis.

The strong collagen fibers of the ECM mainly give mechanical support throughout tissues. Additionally, the carbohydrate chains that form a proteoglycan molecule are very good for absorbing water, and the amount of water differs for particular tissues and can give the matrix a hydrated gel consistency. Therefore, the ECM also serves for resisting compressive forces due to its gel consistency.

Because of its structure, the ECM can work as a physical barrier, an anchorage site, or a movement track for cell migration. The glycoprotein fibronectin functions in cell attachment and migration. Cell migration (movement of cells inside the body or changes in their position) is essential in processes like wound healing and the growth of a fetus.

Integrins are called that way because they integrate or connect the outside and inside of the cell. Their extracellular side binds with the fibronectins, and their cytoplasmic side with the cytoskeleton; they serve functions in cellular communication and signal transmission. Matrix components can activate integrins and change their conformation, which is important, because protein function is directly related to their conformation.

The activated integrin then initiates signaling pathways that affect cell proliferation, differentiation, polarity, contractility, and gene expression. On the other hand, intracellular signals can also activate integrins and trigger signaling to the outside.

Cells can sense the biochemical properties of the ECM, including growth factors and bioactive molecules, and interact accordingly with the outside environment. However, cells can also sense the physical properties of the matrix, like rigidity, density, porosity, and insolubility.