Macromolecular Specificity of Collagen Fibrillogenesis

Abstract

Suprastructures of the extracellular matrix, such as banded collagen fibrils, microfibrils, filaments, or networks, are composites comprising more than one type of macromolecule. The suprastructural diversity reflects tissue-specific requirements and is achieved by formation of macromolecular composites that often share their main molecular components alloyed with minor components. Both, the mechanisms of formation and the final macromolecular organizations depend on the identity of the components and their quantitative contribution. Collagen I is the predominant matrix constituent in many tissues and aggregates with other collagens and/or fibril-associated macromolecules into distinct types of banded fibrils. Here, we studied co-assembly of collagens I and XI, which co-exist in fibrils of several normal and pathologically altered tissues, including fibrous cartilage and bone, or osteoarthritic joints. Immediately upon initiation of fibrillogenesis, the proteins co-assembled into alloy-like stubby aggregates that represented efficient nucleation sites for the formation of composite fibrils. Propagation of fibrillogenesis occurred by exclusive accretion of collagen I to yield composite fibrils of highly variable diameters. Therefore, collagen I/XI fibrils strikingly differed from the homogeneous fibrillar alloy generated by collagens II and XI, although the constituent polypeptides of collagens I and II are highly homologous. Thus, the mode of aggregation of collagens into vastly diverse fibrillar composites is finely tuned by subtle differences in molecular structures through formation of macromolecular alloys.Extracellular matrix aggregates, despite their functional and morphological diversity, often contain the same type of macromolecules as their major constituent. In tendons, for example, large and strongly banded fibrils of variable width are aggregated into bundles that resist extreme tensile forces in one dimension. By contrast, thin fibrils with uniform diameter and spacing are organized into orthogonal sheets forming the translucent corneal stromal matrix that withstands high traction in two dimensions. However, the same protein, i.e. collagen I, is the quantitatively predominant component in both suprastructures (1, 2). The major cartilage collagen is type II, but this protein, too, is common to fibrils with different structures and functions (3, 4). Finally, collagens I and II occur together in fibrocartilage (5), a tissue characterized by a high resistance to both compressive and tensile forces and that contains fibrous bundles in addition to an amorphous extrafibrillar matrix rich in proteoglycans.Collagens I and II are very similar in their molecular structure. They both contain three polypeptides with a central sequence of 1014 amino acids in which strictly every third residue is glycine. In addition, these glycine residues are frequently preceded by hydroxyproline and/or followed by proline. The (Gly-Xaa-Yaa) n sequences are flanked at both ends by short non-periodic sequences, called telopeptide...

Regulation of Collagen Fibril Nucleation and Initial Fibril Assembly Involves Coordinate Interactions with Collagens V and XI in Developing Tendon

“…In addition, collagen XI is expressed during development in a variety of tissues (30, 43, 44). Finally, collagen XI was shown to interact with collagen I to regulate fibril assembly in in vitro assays (45). This work demonstrated that collagens I and XI formed heterotypic fibrils and that in vitro co-assembly of collagens I and XI resulted in the assembly of smaller diameter fibrils.…”

“…Protofibril diameter also is a regulated by collagens V and XI. It is possible that collagens V and XI have different interactions with collagen I resulting in unique composite structures that would result in different fibril structures (45). A decrease in nucleation events and constant collagen I tissue content results in more collagen I assembled into each protofibril resulting in larger diameters.…”

Collagen Suprastructures

“…Thus, collagen I/XI-fibrils are composites containing alloyed cores and sheaths of pure collagen I. Their final morphology is variable and depends on the collagenous composition [8]. Extrapolating this concept to banded fibrils in general, it has now become clear that the mixtures of fibrillar 188 D. E. Birk · P. Bruckner …”

Typ 5-Kollagen im Gelenkknorpel von Mensch und Pferd

“…Types V and XI collagen molecules provide a template around which types I and II molecules aggregate to form fibrils (Eyre 2002, Hansen and Bruckner 2003, Wenstrup et al 2004, Wu et al 2009). Type V collagen is associated with type I collagen and type XI collagen with type II, but, as was mentioned above, some of the molecules are hybrid.…”