What forms the basement membrane?

Basement Membrane Composition

The basement membrane is formed by two independent polymeric networks—one composed of laminin and one of type IV collagen—which are interconnected by linking proteins including nidogen (entactin) and perlecan. 1

Core Structural Components

The basement membrane consists of a bilayered structure (lamina lucida and lamina densa) that is assembled from specific extracellular matrix proteins: 2

Primary Structural Networks

• Type IV collagen forms a self-assembled scaffold network through interactions between specialized N-terminal and C-terminal domains, providing the foundational framework 3
• Laminin-entactin/nidogen complexes self-associate into aggregates that form the second independent polymeric network 3
• These two networks are interconnected, presumably via binding sites on the entactin/nidogen molecule 3

Linking and Anchoring Proteins

• Nidogen (entactin) serves as a critical bridge between the collagen IV and laminin networks 1, 3
• Perlecan (a heparan sulfate proteoglycan) anchors into the membrane and provides clusters of negatively charged groups 3
• Heparan sulfate proteoglycans contribute to the structural integrity and charge-selective properties 4

Additional Basement Membrane Components

Beyond the core structural proteins, basement membranes contain tissue-specific proteins that create biochemically and biophysically distinct structures: 1

• Fibulin, hemicentin, SPARC, agrin, and type XVIII collagen are present in various combinations depending on tissue type 1
• Collagen XVII and integrin α6β4 are transmembrane proteins with extracellular domains extending into the lamina lucida 2
• Laminin 332 is specifically localized to the lamina lucida region 2
• Collagen VII forms anchoring fibrils in the sublamina densa region 2

Cellular Synthesis and Assembly

• Basement membranes are synthesized by cells in close apposition to them, including basal epithelial cells, endothelial cells, muscle cells, and Schwann cells 5
• The collagen component is secreted as a procollagen precursor that interacts with matrix glycoproteins in the extracellular space to form the appropriate structure 5
• Both endothelial cells and pericytes contribute to basement membrane deposition during vascular tube formation, with the membrane deposited between abluminally recruited pericytes and the endothelial cells lining the tubes 2

Tissue-Specific Variations

Specialization of different basement membranes occurs through: 3

• Presence of tissue-specific isoforms of laminin and collagen IV 3
• Particular proteoglycan populations specific to each tissue 3
• Differences in assembly patterns between different membranes 3
• Presence of accessory proteins in specialized basement membranes 3

Clinical Relevance

A common diagnostic pitfall is misinterpreting the basement membrane as pathologic collagen deposition in tangentially sectioned biopsies. 2 Trichrome staining or immunohistochemistry with antibodies against tenascin can distinguish true collagen deposition from normal basement membrane, as tenascin is not present in normal adult basement membranes. 2

The normal subepithelial collagen layer measures approximately 3 μm in thickness, composed primarily of type IV collagen, whereas pathologic collagen bands (as in collagenous colitis) consist predominantly of type VI collagen and tenascin with lesser amounts of collagen types I and III. 2