Fibronectin is a large glycoprotein found in blood plasma and within the intricate network surrounding cells, known as the extracellular matrix. This protein acts as a molecular bridge, linking cells to other components of the extracellular matrix and influencing cellular behavior. Its ability to bind to many different molecules facilitates connections essential for physiological activities.
Fundamental Characteristics
Fibronectin is a high-molecular weight glycoprotein, typically weighing between 500 and 600 kilodaltons. This protein exists primarily as a dimer, composed of two nearly identical subunits connected by a pair of disulfide bonds at one end. Each individual subunit is large, ranging from approximately 230 to 275 kilodaltons.
The structure of each fibronectin subunit is modular, built from repeating units classified into three types: type I, type II, and type III. These modules are arranged in a linear fashion, resembling “beads on a string.” While all three module types share a beta-sandwich structure, type I and type II modules are stabilized by internal disulfide bonds, whereas type III modules do not contain these bonds.
This modular arrangement allows fibronectin to interact with a diverse array of molecules, including cell-surface receptors called integrins, collagen, fibrin, and heparin. The absence of disulfide bonds in type III modules allows them to partially unfold under physical force, contributing to fibronectin’s dynamic roles in the body.
Two main forms of fibronectin are present in vertebrates: soluble plasma fibronectin and insoluble cellular fibronectin. Plasma fibronectin circulates in the blood and is produced by liver cells. Cellular fibronectin is secreted by various cell types, such as fibroblasts, and is organized into insoluble fibers within the extracellular matrix, providing structural support to tissues.
Essential Functions
Fibronectin plays a role in cell adhesion, helping cells attach to their surroundings and to each other. It provides binding sites for integrins, cell surface proteins that act as anchors, allowing cells to grip the extracellular matrix. This interaction is important for maintaining tissue integrity and structure.
The protein also guides cell migration, a process where cells move through tissues during development, repair, and immune responses. Fibronectin creates pathways that cells can follow, directing their movement to specific locations. This organized movement is important for processes like wound healing and embryonic development.
In wound healing, fibronectin is deposited at the injury site, forming a provisional scaffold. This initial matrix helps stop bleeding and provides a temporary structure for migrating cells, such as fibroblasts and endothelial cells, to move into the wound area. Fibronectin’s involvement facilitates the formation of new tissue and the eventual remodeling of the injured site.
Fibronectin also contributes to tissue development and remodeling. It helps organize the extracellular matrix by binding to other components like collagen and proteoglycans, facilitating the formation and maintenance of tissues. Its dynamic nature allows for continuous reorganization of the matrix, important for tissue adaptation and repair.
Beyond structural roles, fibronectin is involved in blood clotting. Plasma fibronectin is rapidly deposited at the site of vessel injury, where it interacts with fibrin to strengthen the blood clot. This interaction helps to stop bleeding and promotes the adhesion and aggregation of platelets, small clot-forming cells.
Role in Health and Disease
Proper fibronectin activity is important for maintaining healthy tissues and processes throughout the body. Its balanced expression and organization contribute to the normal functioning of cell adhesion, migration, and tissue repair mechanisms. When fibronectin’s activity is disrupted, it can contribute to various health conditions.
For example, excessive or altered fibronectin can play a part in fibrotic diseases, which involve the overgrowth and hardening of tissues. In these conditions, abnormal accumulation of fibronectin can lead to scarring and organ dysfunction, as seen in conditions affecting organs like the kidneys.
In the context of cancer, fibronectin can influence tumor growth, invasion, and spread (metastasis). Changes in fibronectin expression or organization have been observed in tumors, where it can promote the movement of cancer cells and their ability to establish new growths in different parts of the body.
Fibronectin also has connections to inflammatory responses. While it is important in the initial stages of wound healing, certain forms or fragments of fibronectin can amplify inflammation. This can occur when fibronectin is altered, potentially contributing to persistent inflammatory states in tissues.
Understanding fibronectin’s specific roles in these disease states opens avenues for potential therapeutic strategies. Researchers are exploring how targeting fibronectin or its interactions could help manage diseases where its function is abnormal, aiming to restore healthy tissue balance.