Collagen Fibril Assembly and Function

Abstract

Collagen fibrils are the major mechanical component in the extracellular matrix of a broad range of multicellular animals from echinoderms to vertebrates where they provide a stable framework for tissues. They form the key tension-resisting element of a complex fiber-composite system that has a tissue-specific hierarchical structure linked to mechanical demands. Remarkably, these tissues are self-maintaining and avoid fatigue failure over the lifetime of the animal. Collagen fibrils can assemble spontaneously from purified solutions of collagen molecules. In developing tissues, however, in addition to the intrinsic self-assembly properties, there is cellular machinery that regulates fibril nucleation, spatial orientation, and fibril size, according to the tissue and stage of development. The intricate mechanisms underlying the generation of a collagen fibril network of defined architecture and mechanical properties are now becoming apparent. Impairment of this system leads ultimately to mechanical failure or tissue fibrosis.

A multi-layered and dynamic apical extracellular matrix shapes the vulva lumen in Caenorhabditis elegans

“…Many secreted matrix proteins are packaged and trafficked via specialized vesicles. For example, collagens are secreted from extra-large vesicles (Malhotra & Erlmann, 2015) and then processed after secretion to enable their assembly (Holmes, Lu, Starborg, & Kadler, 2018).…”

Polarization‐dependent second‐harmonic generation for collagen‐based differentiation of breast cancer samples

“…Such analysis implies that the reduction of the ratio parameter values at higher grades of tumor progression, observed in Figure 5B, could not be attributed to the f, δ angle orientation disorders, indicating that different morphological modifications of the collagen structure occur after the that the focal volume is~3 μm 3 and includes 100 fibrils with mean diameter and length in the order of 200 nm and 1 μm respectively. 53,54 This is considered to be a good approximation for the focusing conditions that were employed (N.A. = 0.8).…”

Revealing the Assembly of Filamentous Proteins with Scanning Transmission Electron Microscopy

“…Collagen is the main structural element of the extracellular matrix of connective tissues, important for force transmission and load-bearing. 26 The morphology of the fibrils and the architecture of collagen fibril networks vary widely among tissues, providing tissue-specific mechanical functions. Reconstitution studies have shown that collagen assembly is regulated by many environmental factors, such as temperature, pH, and ionic strength.…”

“…The absence of these telopeptides results in a loss of diameter uniformity and changes in the fibril assembly pathway. 26,31 Fibrils reconstituted from purified collagen usually exhibit high axial periodicity, but their degree of lateral packing order is still elusive. X-ray diffraction studies in tissue collagen indicate an almost crystalline molecular packing, 27,29,32 but deviations from this model are often observed.…”

“…35 The spatial map of the variation along the fibril furthermore enables us to infer a value for the average D-spacing of <D> = 66.7 ± 5.4 nm, consistent with prior reports based on negative stain EM and AFM. 14,26,31 The ( ) profile shown in Fig. 5D furthermore enables us to directly check the quarter-stagger Fig.…”