The binding capacity of α1β1-, α2β1- and α10β1-integrins depends on non-collagenous surface macromolecules rather than the collagens in cartilage fibrils

Abstract

Interactions of cells with supramolecular aggregates of the extracellular Matrix (ECM) are mediated, in part, by cell surface receptors of the integrin family. These are important molecular components of cell surfacesuprastructures regulating cellular activities in general. A subfamily of β1-integrins with von Willebrand-factor A-like domains (I-domains) in their α-chains can bind to collagen molecules and, therefore, are considered as important cellular mechano-receptors. Here we show that chondrocytes strongly bind to cartilage collagens in the form of individual triple helical molecules but very weakly to fibrils formed by the same molecules.We also find that chondrocyte integrins α1β1-, α2 β1-and α10β1-integrins and their I-domains have the same characteristics. Nevertheless we find integrin binding to mechanically generated cartilage fibril fragments, which also comprise peripheral non-collagenous material. We conclude that cell adhesion results from binding of integrin-containing adhesion suprastructures to the non-collagenous fibril periphery but not to the collagenous fibril cores. The biological importance of the well-investigated recognition of collagen molecules by integrins is unknown. Possible scenarios may include fibrillogenesis, fibril degradation and/orphagocytosis, recruitment of cells to remodeling sites, or molecular signaling across cytoplasmic membranes. In these circumstances, collagen molecules may lack a fibrillar organization. However, other processes requiring robust biomechanical functions, such as fibril organization in tissues, cell division, adhesion, or migration, do not involve direct integrin-collagen interactions.

Crucial Role for Endothelial Cell α2β1 Integrin Receptor Clustering in Collagen‐Induced Angiogenesis

“…Of these, we proposed the central integrin‐binding site to be the most functionally relevant (Sweeney et al, ). Yet, it was possible that in vivo , this site was the only one available for cell interactions during collagen assembly or remodeling (Orgel et al, ; Woltersdorf et al, ). It is of interest to discuss the polyvalent nature of the collagen fibril as it relates to integrin receptor clustering, assuming that at least one of the three integrin‐binding sites is available on the collagen fibril surface.…”

Integrin αVβ3 can substitute for collagen‐binding β1‐integrins in vivo to maintain a homeostatic interstitial fluid pressure

“…It can furthermore not be excluded that the Ha1/29 antibody inhibits both α 2 β 1 and α 11 β 1 . It is not clear whether collagen‐binding β 1 ‐integrins bind directly to collagen molecules in the ECM fibres in vivo or only via accessory proteins as has been suggested to be the case for chondrocyte binding to cartilage collagenous fibres (Woltersdorf et al., ). Our present data do not discriminate between these two possibilities but together with previously reported data show that integrins play an important physiological role in controlling P IF .…”

Routes towards Novel Collagen-Like Biomaterials

“…In addition, fully synthetic genes also allow the direct incorporation of integrin-specific cell adhesion sites, such as the RGD motif and more collagen-typical adhesion sites such as GFOGER-like sequences [73]. When processed into more tightly packed structures such as fibrils and fibers, direct integrin mediated cell adhesion has been shown to be impaired [74], and thus will possibly require more complex solutions to mediate the adhesion between eCol-fibrils and the cells within the ECM. One recently described group of proteins, the so-called COLIBRIs (COLlagen INtegrin BRIdging proteins) [75,76], which form a bridge between natural fibrillar collagen and integrin including the well-known proteins fibronectin and von Willebrand factor, might be able to fulfill this role.…”