Restraining Cross-Links Responsible for the Mechanical Properties of Collagen Fibers: Natural and Artificial

Abstract

The mechanical properties of collagen fibers primarily depend on the formation of head to tail Schiff base cross-links between end-overlapped collagen molecules within the fiber induced by the enzyme lysyl oxidase. Inhibition of these cross-links results in the complete loss of mechanical strength of the fiber. During maturation these initial divalent cross-links react further with molecules in register from an adjacent fiber forming stable trivalent cross-links and further increasing its mechanical strength. This system of cross-linking is well established and exists throughout the animal kingdom from sponges to man, but there remain a number of unidentified cross-links known to be present in some tissues. In addition, there are some unusual cross-links in certain invertebrates. The nature of the collagen cross-linking is tissue specific rather than species specific and depends on the extent of hydroxylation of both the telopeptide and triple helical lysines involved in the cross-link and on the rate of collagen metabolism. The cross-link profile of collagen fibers therefore varies considerably within and between tissues, for example in different bones. Recent studies indicate that pyrrole cross-links rather than pyridinoline cross-links correlate with mechanical strength of avian bones. The profile can change between normal loading and extreme exercise and these differences appear to relate to their particular function, but further studies to identify whether a particular cross-link is responsible remain to be carried out.Following maturation the low turnover of collagen allows the non-enzymic random accumulation of glucose oxidation products, some of which form intermolecular cross-links, ultimately rendering the fiber too stiff for normal function. The significance of the major glycation cross-link, believed to be glucosepane, remains to be confirmed. The successful use of inhibitors of this glycation reaction and of specific glycation cross-link breakers should lead to a reduction in this deleterious effect in both aging and diabetes mellitus.The high mechanical strength and resistance to heat and bacterial degradation of collagen fibers has been utilized industrially. Additional chemical cross-linking in vitro has been employed historically to attain specific mechanical and thermal properties, for example tanning skin to leather, and more recently in medical and cosmetic products with low cytotoxic effects. The resultant increases in denaturation temperature have recently been correlated with reduced water content of the fiber.

Muscle fascia and force transmission

“…Advanced glycation end products can be incorporated into the body from dietary sources (e.g. heat processing of some foods creates AGEs) and from tobacco smoke (Avery and Bailey, 2008). In this way, diet and lifestyle may affect the mechanical properties of IM-ECM via AGE-cross-linking of collagens.…”

Tissue Transglutaminase, Not Lysyl Oxidase, Dominates Early Calcium-Dependent Remodeling of Fibroblast-Populated Collagen Lattices

“…LOX oxidizes select lysines within collagen to form aldehydes that react to form covalent bonds and stabilize the molecules within fibers [Kagan, 2000]. The absence of LOX-mediated cross-linking in vivo results in weak collagen fibers and fragile collagenous tissues [Avery and Bailey, 2008]. tTG cross-links a number of extracellular matrix proteins, including type I collagen, primarily through the formation of an Nε(γ-glutamyl)lysine bond between two molecules [Wang and Griffin, 2012].…”

Collagen-Immobilized Lipases Show Good Activity and Reusability for Butyl Butyrate Synthesis

“…The pore volume was found to decrease after glutaraldehyde modification, and the values are 0.0049, 0.0026, and 0.0041 cm 3 /g for native, glutaraldehydeactivated, and lipase-loaded collagen fibers, respectively. The reduction in pore volumes of glutaraldehyde-activated and lipase-loaded samples may be because the distance between the collagen fibers is shortened after the modification of glutaraldehyde [42]. The morphologies of native, activated, and lipase-immobilized collagen fiber were observed via SEM.…”