Connective Tissue Formation in Wound Healing - E-thesis

folding and association into a triple helix requires the involvement of molecular chaperone
(60). After formation of the major triple helix the N-terminal propeptide will be assembled
(54). Pro-collagens are secreted out of the cell, where they are converted to collagen by
proteolytic cleavage of both the N-and C-terminal propeptide extensions. N-terminal
propeptide is cleaved by the collagen type-specific N-proteinases. For maximal N-proteinase
activity, all three chains of the collagen molecule must be in register. C-terminal proteinases
also appear to be collagen-type specific but they does not require the intact trimer as the
substrate. After removal of the propeptides the collagen monomers spontaneously assemble
into fibrils by an entropy-driven process. Once the fiber is formed, the associations are
stabilized by intermolecular crosslinks that provide the fiber with tremendous tensile strength
and insolubility. Most of the cross-links form between the telopeptides at each end of collagen
molecules. Collagen fibril formation is a complex process that is regulated by a number of
different factors, including the collagen type present, the sequence and extent of propeptide
processing, interactions with other matrix components such as proteoglygans, as well as a
direct involvement of the cells (61).
Fibrillar collagens
Based on their protein and gene structures, types I, II, III, V, and XI collagens have been
assigned to the fibril-forming group (58). They all contain a globular N-terminal domain that
includes a short triple helical sequence, a major uninterrupted triple helical domain of
approximately 1000 amino acids and a globular C-terminal domain. These collagens can be
divided into two groups, major (I, II and III) and minor fibrillar collagens (V and XI), based on
the quantities of proteins in tissue. Type II and XI collagens are found mainly in cartilaginous
tissue. In connective tissues, other than cartilage, collagen fibrils are mainly composed of type I
III and V collagens at different molecular rations, with diameters ranging from 20 to 500 nm
(57). Fibrillar collagen molecules are either homotrimers with α-chains of the same kind or
heterotrimers composed of two or three different α-chains. These α-chain molecules consist of
an uninterrupted triple helix of approximately 300 nm in length and 1.5 nm in diameter flanked
by short extra-helical telopeptides. The lateral interaction between the homologous regions
within the triple helical domains is the basis for fibril formation. Fibrillar collagens selfassemble
into cross-striated fibrils observed in electron microscopy in negatively stained fibrils
(Fig. 2.)
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