In praise of dyestuff histochemistry

The merits of low molecular weight reagents (mini-stains) for localising tissue components, are compared with those of high molecular weight (macro-stains), with respect to stoichiometry, ease of tissue penetration, and particularly specificity. Macro-stains, which are based mainly on antibodies, are likely to be more specific, but this will not always be the case. The concept of specificity in the design of mini-stains is examined, and its application to the delivery of e.g. Cupromeronic blue to particular substrates in the "critical electrolyte concentration" system, is discussed. The much greater resolving power of mini-stains in electron histochemistry has permitted the elucidation of four specific binding sites for proteoglycans along the collagen fibrils, validating the 'one proteoglycan: one binding site' hypothesis.