Fibronectin is a large protein found throughout the body, serving as a versatile component in various biological processes. It is a significant element of the extracellular matrix (ECM), the network of molecules providing structural and biochemical support to cells. This protein plays a role in numerous functions, including cell adhesion, growth, movement, and cell specialization. Its presence is particularly notable in processes like wound healing and embryonic development.
Fibronectin’s Molecular Identity
Fibronectin is a high-molecular-weight glycoprotein, a protein with attached carbohydrate chains. It exists as a dimer, composed of two nearly identical polypeptide chains, each with a molecular weight ranging from approximately 230 to 275 kDa. These two subunits are linked by a pair of disulfide bonds at their C-terminal ends.
Each fibronectin subunit contains multiple repeating modules: type I, type II, and type III. All three module types feature a beta-sandwich structure. Type I and type II modules are stabilized by internal disulfide bonds, while type III modules lack these bonds, allowing them to partially unfold when subjected to force. Fibronectin is found as an insoluble component within the extracellular matrix of tissues and in a soluble form in blood plasma.
The two main forms, cellular fibronectin and plasma fibronectin, differ in several ways. Plasma fibronectin, produced by liver cells (hepatocytes), circulates in the blood plasma in a compact, inactive form and lacks certain alternative spliced regions (EDA and EDB) found in cellular fibronectin. Cellular fibronectin, synthesized by various cells like fibroblasts, endothelial cells, and macrophages, is assembled into an insoluble fibrillar network within the extracellular matrix.
Core Functions in the Body
Fibronectin plays fundamental roles in how cells interact with their environment. Its primary function is mediating cell adhesion, enabling cells to attach to the extracellular matrix. This occurs through specific binding to cell surface receptors called integrins, which then link to the cell’s internal cytoskeleton.
Fibronectin is also involved in cell migration, the directed movement of cells. It provides a temporary scaffold that guides cell movement during processes like embryonic development and tissue repair. The interaction between fibronectin and integrins helps control cell adhesion, which drives cell migration.
Fibronectin also influences cell differentiation, the process by which cells develop into specialized types. It can act as a structural scaffold, providing an environment for cell adhesion and differentiation, or it can signal through integrins to activate internal cellular pathways that regulate gene expression during differentiation. The fibronectin matrix supports the deposition of other extracellular matrix proteins, contributing to tissue organization.
Fibronectin in Wound Healing and Tissue Repair
Fibronectin plays a significant role in wound healing and tissue repair from the initial moments of injury. Immediately following tissue damage, plasma fibronectin from the bloodstream leaks into the wound site and becomes a major component of the forming blood clot. This initial fibronectin, along with fibrin, helps form a temporary scaffold that stops bleeding and protects the underlying tissue.
This provisional matrix, rich in fibronectin, provides a surface for the adhesion and migration of cells necessary for repair, such as fibroblasts. Fibroblasts adhere to this fibronectin-fibrin network, which is particularly strong when fibronectin is cross-linked to fibrin. As healing progresses, fibroblasts and other cells synthesize and assemble cellular fibronectin into a more organized, insoluble matrix.
The fibronectin scaffold also serves as a reservoir for growth factors, accumulating them locally to support the proliferation and differentiation of cells involved in tissue regeneration. As the wound heals, this temporary fibronectin matrix is gradually degraded, a process necessary for complete tissue remodeling and recovery.
Clinical Significance
The proper functioning of fibronectin is important for maintaining tissue integrity throughout the body. Its roles in cell adhesion, migration, and differentiation contribute to healthy physiological processes, including the ongoing maintenance and repair of tissues. When fibronectin’s regulation or structure is disrupted, it can have broader implications for health.
Imbalances in fibronectin expression, its breakdown, or its organization have been linked to various conditions where tissue integrity is compromised. This underscores fibronectin’s role in supporting normal biological functions and how its proper regulation contributes to tissue health.