Letter to the editor

Mucin subunits linked by disulphide bridges?

Mucins represent the main components of gel-like secretions, or mucus, secreted by mucosae or some exocrine glands. These high-molecular-weight glycoproteins are characterized by the large number of carbohydrate chains O-glycosidically linked to the peptide.

The determination of mucin molecular weight and conformation has been controversial for several reasons: 1) the methods used to solubilize mucus and to purify mucins are different and 2) the molecules have a strong tendency to aggregate or to bind to other molecules (peptides or lipids). Recently, electron microscopy has shown the filamentous shape of most mucins and their polydisperse character which, in some secretions, might correspond to a polymorphism of the peptide part of these molecules.

The recent development of high pressure liquid chromatography and high-resolution proton NMR spectroscopy has allowed major progress in the structural study of mucin carbohydrate chains. These chains may have from 1 to about 20 sugars and bear different antigenic determinants, such as A, B, H, I, i, X, Y or Cad antigens. In some mucins, such as human respiratory mucins, the carbohydrate chain diversity is remarkable, which raises many questions.

Mucins are molecules located at the interface between mucosae and the external environment. The carbohydrate chain diversity might allow many interactions between mucins and microorganisms and play a major role in the colonization or the defense of mucosae.

This chapter discusses the electron microscopy of individual molecules. Development of methods by which individual macromolecules and their polymers can be visualized at the limit of microscopic resolution is centrally important to a burgeoning range of applications of the electron microscope to biochemical problems. Adequate specimen contrast and stability, especially against beam damage, are basic requirements. Although observation of biological specimens in an approximately native state, even at moderate resolutions, is a major concern of microscopy, prospects for extending ultimate resolution continue to be a subject of compelling interest to cell biology. Since 1960, the ultimate resolution obtained in images of biological objects has been extended from about 2.0nm to 0.35nm, the latter being achieved only by combining microscopy with image processing and crystallographic techniques. Specimen damage resulting from the high electron intensities needed, at magnifications capable of revealing ultimate resolution, is a severe limitation in biological electron microscopy.