Metachromasia

This depends on the charge density of the negative sulfate and carboxylate anions in the glycosaminoglycan (GAG).

Thus, hyaluronic acid, lacking sulphate groups and with only moderate charge density, causes slight metachromasia; chondroitin sulfate, with an additional sulfate residue per GAG saccharide dimer, is an effective metachromatic substrate, whilst heparin, with further N-sulfation, is strongly metachromatic.

Humbel and Etringer's original assay was developed by others to create a stable and widely used dimethylmethylene blue reagent.

Although metachromasia was observed and described since 1875, by Cornil, Ranvier and others, it was the German scientist Paul Ehrlich (1854-1915) who gave its name and studied it more extensively.

The modern understanding of metachromasia was advanced by Belgian histologist Lucien Lison, who studied it between 1933 and 1936 and ascertained its value in the quantitative determination of sulfate esters of high molecular weight.