Fibronectin: A Cell Adhesion and Blood Clotting Protein
An Essential Protein in the Body
Fibronectin is an interesting and essential protein in our body. It has both adhesive and elastic properties, which makes it very useful. Fibrils made of fibronectin attach cells to the medium that surrounds them. This medium is known as the extracellular matrix, or ECM. Fibronectin fibrils also control important aspects of cell behavior and help to stop bleeding when we're injured. In addition, they attach the amniotic sac containing the fetus to the lining of the uterus.
Types of Fibronectin
Cellular fibronectin is secreted by specialized cells in the ECM called fibroblasts as well as by some other cell types. It attaches tissue cells to components of the extracellular matrix and also influences the behavior of the cells.
Plasma fibronectin is made by liver cells, or hepatocytes. It enters the blood in a compact and inactive form. When we're wounded, it changes into a fibrillar form and become active. This type of fibronectin helps to form the blood clot that stops bleeding.
Fetal fibronectin is a special type of cellular fibronectin that is made by cells of a fetus, as its name suggests. The fetus is enclosed in the amniotic sac. Fibronectin fibrils attach the amniotic sac to the lining of the uterus, keeping the developing baby safely in place.
The word fibronectin comes from the Latin words "fibra", which means fiber, and "nectere", which means tie or bind. The name is appropriate, since a major function of the protein is to join structures together.
A protein is made of amino acids that are joined together to make a chain. The chain of amino acids is called a polypeptide. Fibronectin is made of two polypeptides, which lie beside each other and are attached by a pair of bonds at the end of each amino acid chain.
Fibronectin is a glycoprotein—one which has one or more carbohydrate chains attached to a polypeptide. Like other proteins, a fibronectin molecule is folded into a complex, three dimensional shape.
Structure and Function of the Polypeptide
Researchers have discovered that a polypeptide in a fibronectin molecule contains "domains". A domain is a region of the polypeptide that can join to a specific molecule. Domains may join to a chemical in the extracellular matrix, a chemical in blood, or another fibronectin molecule (often symbolized as FN or Fn). Some domains join to specific types of cell membrane receptors. The domains enable fibronectin to be "sticky".
Like many other aspects of cell biology, the structure and behavior of fibronectin is complex and not completely understood. The exploration of the chemical's actions could be very helpful in understanding some health disorders as well as normal activity in the body.
Extracellular Matrix in Bone
The Extracellular Matrix or ECM
An extracellular matrix, or ECM, is present outside and next to cells. This matrix is made of an organized arrangement of protein fibers embedded in a hydrated polysaccharide gel. The proteins include collagen, which provides strength, elastin, which provides elasticity, and fibronectin. A "polysaccharide" is a type of carbohydrate and is made of a chain of monosaccharide (simple sugar) molecules.
The ECM is often specialized is some way. For example, in bones the matrix is strengthened and solidified with calcium salts. The ECM in tendons and ligaments is loaded with collagen fibers, producing a ropy texture. Tendons connect muscles to bones while ligaments connect one bone to another at a joint.
It was once thought that the only functions of the extracellular matrix were to form a type of scaffold to support and protect the body's organs and to connect parts of the body together. Researchers now know that it also regulates the behavior of cells and plays an active role in their lives.
The extracellular matrix contains protein fibres and a polysaccharide gel. Connective tissue is extracellular matrix containing cells.
The extracellular matrix is secreted by specialized cells. These cells are often present in the ECM but are often widely separated from each other instead of being close together as most cells are. "Connective tissue" is the name used for extracellular matrix that contains cells.
Fibroblasts are the most common cells in extracellular matrix and secrete the different kinds of proteins and polysaccharides found in the matrix. Bone is produced by osteoblasts and cartilage is made by chondrocytes, however.
Cellular fibronectin is made by several types of cells, including fibroblasts, macrophages (a type of white blood cell), endothelial cells (which line the inside of blood vessels), and some epithelial cells (which cover surfaces and line hollow organs). Endothelium is often considered to be a special type of epithelium.
Fibronectin is released into the extracellular matrix in a folded and inactive form. It joins to cell membrane proteins called integrins. Here the fibronectin molecules unfold and are assembled into three dimensional networks, which are active.
Cellular fibronectin plays an important role in cell adhesion. Fibronectin networks join to cell membrane integrin molecules and attach the cells to components of the ECM, such as collagen fibers.
Cellular fibronectin has functions beyond simple adhesion. Integrins extend all the way through the cell membrane and interact with structures inside the cell. By binding to integrins, fibronectin can influence cell activities. It guides the movement of cells as they migrate during embryonic development. Fibronectin also plays a role in cell growth, differentiation (specialization), and proliferation. Its fibrils can stretch up to four times their resting length as they carry out their functions.
Plasma is the liquid component of blood. Blood is a special kind of connective tissue in which the cells are suspended in a liquid medium instead of a polysaccharide gel.
A compact, non-functional form of fibronectin is dissolved in plasma and circulates around the body in the bloodstream. When someone is wounded, another soluble protein in blood plasma called fibrinogen is converted to solid fibrin threads. These threads form a mesh over the wound, stopping blood loss. Plasma fibronectin located around the clot extends into a fibrous form and becomes active. Fibronectin fibrils are added to the clot to provide stability. They also promote platelet adhesion. Platelets stick together within a clot to help stop blood flow.
The amniotic sac is a fluid-filled container that has a wall made of a double layer of membrane. The fluid cushions and protects the baby. Fibronectin fibrils attach the amniotic sac to the lining of the uterus. Some fibronectin may leak into the birth canal during the first 22 weeks of pregnancy as new attachments are being made in the uterus and fibronectin is being produced. Between about 24 and 35 weeks, however, no fibronectin should be detected in the birth canal. After this time it appears again as attachments start to weaken in preparation for birth.
Fetal fibronectin is often thought of as a type of glue that "sticks" the amniotic sac to the uterine lining.
The Fetal Fibronectin Test
Women who are at risk for a preterm labor may receive a fetal fibronectin test (or tests) starting at round 23 or 24 weeks of pregnancy. A swab is used to obtain fluid from inside the birth canal near the cervix. The fluid is then tested for the presence of fibronectin. The results of the test can be ready in as little as an hour if necessary but are generally available within a few hours.
If no fibronectin is detected, there is a 99% probability that the woman won't go into labor within the next two weeks. Unfortunately, the significance of a positive test is not so certain. It indicates an increased risk of labor in the next couple of weeks, but the premature labor may not happen. Doctors may test at-risk women every two weeks from around 24 weeks of pregnancy to about 35.
The advantage of knowing that a premature delivery is imminent is that corticosteroids can be given to the mother to improve the lung function of her immature fetus. Medication can also be given to reduce the chance of a preterm labor.
A Test for Premature Labor
An Important Molecule
Studying fibronectin is an important endeavor. Fibronectin influences vital aspects of cell biology, which in turn influences our body's functions. It's also important in preventing blood loss and in wound healing.
Scientists are discovering an increasing number of functions of both fibronectin and the extracellular matrix. They are far more important than was once realized. Studying fibronectin's structure and discovering what the protein does should help researchers discover its role in both health and disease.
© 2013 Linda Crampton