The first and second 'laws' of chemical morphology, exemplified in mammalian extracellular matrices.

Abstract

Tissues are supramolecular organisations. The permanent and semi-permanent biopolymers therein function collaboratively in specifically bonded frameworks of macromolecules according to the physico-chemical laws that govern the behaviour of all molecules. In this paper two 'laws' or principles are discussed which give insights into the development and function of tissues, particularly the extracellular matrices (ECMs) of connective tissues. The first 'law' is qualitative;- The shape of a tissue is implicit in the shapes of the biopolymers from which it is constructed. The tissue biopolymers are jigsaw pieces, if they don't fit precisely, there is no picture. The second 'law' is quantitative;-The composition of a tissue is determined by the stable, specific interactions between the macromolecules of which it is constructed. These basic ideas underlie the discipline of chemical morphology. The term chemical morphology implies both the chemistry of shape and the shape of chemicals. The first meaning is well exemplified in the ECMs of connective tissues, in which the shape of an organism is defined and maintained. Specific relationships between the fibrillar (collagenous) components and the soluble polymers (proteoglycans) are set in the context of the first law. Tissue electron histochemistry (the morphology of the tissue) and knowledge of secondary and tertiary structures of the participating biopolymers (the shapes of the chemicals) together provide a model susceptible to quantitative testing. Simple calculation shows that the amount of any ligand (e.g. a proteoglycan) specifically bound at a single binding site per unit of collagen fibril length (the D period) increases linearly with the fibril diameter. Given the amount of collagen (measured as hydroxyproline) and its density, the constant of proportionality is approximately 42. Comparisons of the quantitative relationship between collagen and proteoglycans predicted from the model agree well with those obtained by biochemical analyses of different tendons from three species at all stages of development. Thus, the second 'law' appears to hold in this case.