Assembly of Basement Membranes a

A goal in the study of basement membranes is to elucidate matrix molecular and supramolecular structure in three-dimensional space and learn how that structure is related to function. The formation of basement membrane matrix from its component macromolecules appears, to a great extent, to be that of self-assembly’-that is, protomers, or molecular “building blocks,” can spontaneously and specifically bind to themselves in an extracellular space by mass action to form functional supramolecular architectures. The process of assembly is clearly complex. Individual components are large (130-850 kDa) and subdivided into a number of structural domains. There appears to be an array of binding interactions: both lowand high-affinity noncovalent ones as well as covalent cross-links that form following matrix deposition. Analogous to the situation in the red cell cytoskeleton: there may be a coupling of strong and weak interactions such that the strong ones place the various macromolecules into high local concentration, permitting weaker interactions to contribute to final structure and function. In the EHS (Engelbreth-Holm-Swarm) basement membrane, the concentrations of the major components (collagen and laminin) are 11 13 p M (TABLE 1 ), and interactions with dissociation constants smaller than this value could contribute to structure. Type IV collagen, laminin, entactin (nidogen), and several heparan sulfate proteoglycans are unique intrinsic structural components of basement membranes. The first two of these are capable of forming polymers and of interacting with each other through an entactin/nidogen bridge, and probably associate directly as well. A large heparan sulfate proteoglycan binds laminin and interacts with itself to form oligomers. In concert, these units appear important for the formation of functional basement membranes. Basement membrane matrices can also be found in association with SPARC (osteonectin), fibronectin, proteins unique to specific basement membranes, minor (mostly uncharacterized) components, and growth factors that can adhere to heparan sulfate. While these latter components undoubtedly contribute to function, their architectural significance is unclear. Major functions of basement membranes dependent on the above are those of cell support, selective molecular sieving, and the ability to bind to cells and regulate their