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Cell-matrix interactions involving collagen include a wide range of classical receptor-ligand mediated signaling pathways. Nonetheless the main functional feature of most collagens (this review will focus on type-I collagen) is mechanical load bearing of tensile force. The mechanical function of any connective tissue results from often highly sophisticated architectural arrangement of collagen substructures, along with other elastic extracellular matrix proteins such as elastin, and water binding proteoglycans. Although soft connective tissues of the body are composed of nearly identical basic molecular building blocks, their varied arrangement makes possible an exquisite range of potential tissue mechanical properties. The cells that mediate the functional assembly of these building blocks do so according to their epigenetic pre-program as guided by the mechanical demands on the tissue.
Within any collagenous connective tissue, the functional building blocks that provide tensile strength and elasticity are called collagen “fibrils”. The collagen fibril is a helically arranged supramolecular structure that can range in diameter from a few to several hundred nanometers, with lengths that can run on the order of centimeters. How collagen molecules are accrued into these structures (a process known as fibrillogenesis) relies on sequences of elegant intracellular and extracellular events that, while fascinating, are outside the scope of the present review. Current evidence suggests that the mature collagen fibrils resulting from fibrillogenesis are highly elastic structures – meaning that they mechanically load and unload in a mostly reversible fashion. To be able to reversibly load and unload, without damage, is the defining functional requirement of these protein superstructures. Collagen cross linking is a central enabler (and potential disabler) of this function.