Collagen Cross-Linking

  • Marvin L. Tanzer
Part of the NATO ASI Series book series (NSSA, volume 93)


The structural macromolecules of the extracellular matrix have been investigated with rapidly increasing activity and depth in the past decade. Collagen, and to a lesser extent, elastin, were among the earliest of this group to be studied in more detail than the proteoglycans and adhesive glycoproteins. Consequently, the extent of knowledge concerning collagen is greater than any of the other structural macromolecules; one index of this phenomenon is the large number of symposia and monographs which have been devoted to collagen in the past generation. One can virtually trace an exponential growth curve of the literature concerning the structure, function and biological properties of the protein. Probably such extensive interest reflects the great abundance of collagen, its widespread industrial applications, its purported roles in developmental biology, its phylogenetic diversity, and its primary role as the major structural polymer of most animal tissues.


Collagen Molecule Lysyl Oxidase Byssal Thread Bovine Articular Cartilage Collagen Polymer 


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  1. Adams, E., 1978, Invertebrate collagens, Science, 202:591.ADSCrossRefGoogle Scholar
  2. Bailey, A.J., 1968, Intermediate labile intermolecular crosslinks in collagen fibres, Biochim. Biophys. Acta, 160:447.Google Scholar
  3. Bailey, A.J., Ranta, M.H., Nicholls, A. C., Partridge, S. M., and Elsden, D. F., 1977, Isolation of α-amino adipic acid from mature dermal collagen and elastin. Evidence for and oxidative pathway in the maturation of collagen and elastin, Biochim. Biophys. Res. Commun., 78:1403.Google Scholar
  4. Banes, A.J., Yamauchi, M., and Mechanic, G. L., 1983, Nonmineralized and mineralized compartments of bone: The role of pyridinoline in nonmineralized collagen, Biochem. Biophys. Res. Commun., 113:975.Google Scholar
  5. Becker, U., Furthmayr, H., and Timpl, R., 1975, Tryptic peptides from the cross-linking regions of insoluble calf skin collagen, Hoppe-Seyler’s Z. Physiol. Chem., 356:21.Google Scholar
  6. Blumenfeld, O. O., and Gallop, P.M., 1966, Amino aldehydes in collagen: The nature of a probable crosslink, Proc. Natl. Acad. Sci. U.S.A., 56:1260.Google Scholar
  7. Brown, C. H., 1952, Some structural proteins of Mytilus edulis, Quart. J. Microsc. Sci., 93:487.Google Scholar
  8. Cheung, D.T., Dicesare, P., Benya, P.D., Libaw, E., and Nimni, M. E., 1983, The presence of intermolecular disulfide cross-links in type III collagen, J. Biol. Chem., 258:7774.Google Scholar
  9. Davis, N. R., Risen, O. M., and Pringle, G. A., 1975, Stable, nonreducible cross-links of mature collagen, Biochemistry, 14: 2031.CrossRefGoogle Scholar
  10. Eyre, D.R., 1981, Crosslink maturation in bone collagen, in: “The Chemistry and Biology of Mineralized Connective Tissues,” A. Veis, ed. Elsevier/North-Holland, New York.Google Scholar
  11. Eyre, D. R., Koob, T. J., and Van Ness, K. P., 1984, Quantitation of hydroxypyridinium crosslinks in collagen by high performance liquid chromatography, Anal. Biochem., 137:380.Google Scholar
  12. Franzblau, C., Kang, A.H., and Faris, B., 1970, In vitro formation of intermolecular crosslinks in chick skin collagen, Biochem. Biophys. Res. Commun., 40:437.Google Scholar
  13. Fujimoto, D., 1982, New crosslinks of collagen, Biochemistry (Japan), 54:314.Google Scholar
  14. Fujimoto, D., Akiba, K.-Y., and Nakamura, N., 1977, The structure of pyridinoline, a collagen crosslink, Biochem. Biophys. Res. Commun., 76:1124.Google Scholar
  15. Heathcote, J. G., Bailey, A. J., and Grant, M. E., 1980, Studies on the assembly of the rat lens capsule. Biosynthesis of a crosslinked collagenous component of high molecular weight, Biochem. J., 190:229.Google Scholar
  16. Heathcote, J. G., Eyre, D. R., and Gross, J., 1982, Mature bovine Descemet’s membrane contains desmosine and isodesmosine, Biochem. Biophys. Res. Commun., 108:1588.Google Scholar
  17. Henkel, W., and Glanville, R.W., 1982, Covalent crosslinking between molecules of type I and type III collagen, Europ. J. Biochem., 120:205.Google Scholar
  18. Housley, T., and Tanzer, M.L., 1975, Collagen crosslinking: Isolation of hydroxyaldol-histidine, a naturally-occuring crosslink, Biochem. Biophys. Res. Commun., 67:824.Google Scholar
  19. Katz, E. P., and Li, S.-T., 1981, The molecular packing of type I collagen fibrils, in: “The Chemistry and Biology of Mineralized Connective Tissues,” A. Veis, ed., Elsevier/North Holland, New York.Google Scholar
  20. Light, N.D., and Bailey, A. J., 1980, Polymeric C-terminal crosslinked material from type I collagen. A modified method for purification, anomalous behaviour on gel filtration, molecular weight estimation, carbohydrate content and lipid content, Biochem. J., 189:111.Google Scholar
  21. McBride, O.W., and Harrington, W.F., 1967, Ascaris cuticle collagen: On the disulfide cross-linkages and the molecular properties of the subunits, Biochemistry, 6:1484.Google Scholar
  22. Mechanic, G., Gallop, P.M., and Tanzer, M. L., 1971, The nature of crosslinking in collagen from mineralized tissues, Biochem. Biophys. Res. Commun., 45:644.Google Scholar
  23. Miller, A., 1984, Collagen: The organic matrix of bone, Phil. Trans. R. Soc. Lond. B., 304:455.Google Scholar
  24. Miyoshi, M., Kanamori, M., and Rosenbloom, J., 1976, Synthesis of elastin. A rapid formation of lysine-derived crosslinks by chick embryo aorta, J. Biochem, 79:1235.Google Scholar
  25. Morrison, M., Steele, W., and Donner, D. J., 1969, The reaction of benzoquinone with amines and proteins, Arch. Biochem. Biophys., 134:515.Google Scholar
  26. Murray, L. W., and Tanzer, M. L., 1983, Characterization of a large fragment from annelid cuticle collagen and its relationship to the intact molecule, Collagen Rel. Res., 3:445.Google Scholar
  27. Nimni, M., 1983, Collagen: Structure, Function and Metabolism in normal and fibrotic tissues, Semin. Arthritis Rheum., 13:1.Google Scholar
  28. Pierpont, W. S., 1969, O-quinones formed in plant extracts: Reaction with amino acids and peptides, Biochem. J., 112:609.Google Scholar
  29. Robins, S. P., and Duncan, A., 1983, Cross-linking of collagen. Location of pyridinoline in bovine articular cartilage at two sites of the molecule, Biochem. J., 215:175.Google Scholar
  30. Sakura, S., Fujimoto, D., Sakamoto, K., Mizuno, A., and Motegi, K., 1982, Photolysis of pyridinoline, a cross-linking amino acid of collagen, by ultraviolet light, Can. J. Biochem., 60:525.Google Scholar
  31. Sandberg, L. B., Soskel, N. T., and Wolt, T. B., Structure of the elastic fiber: An overview, J. Invest. Dermatol., 79 Suppl. 1:128S.Google Scholar
  32. Shapiro, F., Brickley-Parsons, D., and Glimcher, M. J., 1979, Biosynthesis of collagen crosslinks in rabbit articular cartilage in vivo, Arch. Biochem. Biophys., 198:205.Google Scholar
  33. Scott, P. G., Veis, A., and Mechanic, G., 1976, The identity of a cyanogen bromide fragment of bovine dentin collagen containing the site of an intermolecular cross-link, Biochemistry, 15:3191.CrossRefGoogle Scholar
  34. Siegel, R. C., 1976, Collagen cross-linking. Synthesis of collagen cross-links in vitro with highly purified lysyl oxidase, J. Biol. Chem., 251:5786.Google Scholar
  35. Stimler, N. P., and Tanzer, M. L., 1977, Location of the intermolecular cross-linking sites in collagen, in: “Protein Crosslinking-B,” M. Friedman, ed., Plenum, New York.Google Scholar
  36. Tanzer, M. L., 1967, Collagen crosslinks: Stabilization by borohydride reduction, Biochim. Biophys. Acta. 133:584.Google Scholar
  37. Tanzer, M. L., 1973, Cross-linking of collagen, Science, 180:561.ADSCrossRefGoogle Scholar
  38. Tanzer, M. L., 1976, Cross-linking, in: “Biochemistry of Collagen”, G.N. Ramachandran, and A.H. Reddi, eds., Plenum, New York.Google Scholar
  39. Tanzer, M. L., 1978, The biological diversity of collagenous proteins, Trends Biochem. Sci., 3:15.Google Scholar
  40. Tanzer, M. L., and Waite, J. H., 1982, Collagen cross-linking, Collagen Rel. Res., 2:177.Google Scholar
  41. Threadgold, L.T., 1957, A histochemical study of the shell gland of Scyliorhinus canicula, J. Histochem. Cytochem., 5:159.Google Scholar
  42. Waite, J.H., and Tanzer, M. L., 1981, The polyphenolic substance of Mytilus edulis. A novel adhesive containing L-DOPA and Hydroxyproline, Science, 212:1038.Google Scholar
  43. Waite, J. H., unpublished.Google Scholar
  44. Wu, J.-J., and Eyre, D. R., 1984, Identification of hydroxypyridinium cross-linking sites in type II collagen of bovine articular cartilage, Biochemistry, 23:1850.CrossRefGoogle Scholar
  45. Yamauchi, M., Noyes, C., Kuboki, Y., and Mechanic, G. L., 1982, Collagen structural microheterogeneity and a possible role for glycosylated hydroxylysine in type I collagen, Proc. Natl. Acad. Sci. U.S.A., 79:7684.Google Scholar

Copyright information

© Plenum Press, New York 1985

Authors and Affiliations

  • Marvin L. Tanzer
    • 1
  1. 1.Department of BiochemistryUniversity of Connecticut Health CenterFarmingtonUSA

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