Ocular Mucin Biophysics

A soft mucus gel coats and protects the surfaces of wet epithelia where the body encounters its environment: the surfaces of eye, mouth, nose, respiratory and digestive systems, and more. Mucins, very large molecules whose peptide core is richly decorated with sugars, form the backbone of these mucus gels, where they interact with bacteria and viruses on the one hand, and with epithelial cells and cells of the immune system on the other.

Along the peptide core, sugars chains are very dense in places, and sparse in others giving a mucin the appearance of a necklace of pearls, as shown, left, for a more than 5 µm long human ocular mucin molecule imaged by Atomic Force Microscopy. Epithelial mucins come in two flavours, secreted, and cell surface bound. The mucin subunit of the latter  is cleaved into the overlying fluid. Mucins spanning the cell membrane convey information to the inside of the cell.

Changes in mucins are associated with disease in some organs e.g. breast and colon – MUC1, the first mucin discovered, has been the focus of research for its connection with breast cancer. In very severe dry eyes there is a decrease in goblet cells, cells which synthesise, store and secrete MUC5AC.

Sugar chains, in particular the last or last few sugars in the chain is what a microorganisms see on a mucin molecule or gel: bacteria and viruses are very choosy in their sweet epitopes. An alteration in the charge or type of sugars can have a large effect on the resident microflora.

The general structure of mucins, is conserved throughout the body, yet details are atuned to the site of secretion. For example, gastric mucins have long oligosaccharide chains, while at the ocular surface sugar chains are short.

The lynch-pin of this research has been understanding how the behaviour of molecules in a complex fluid is affected by alterations in their biophysical  and biochemical characteristics. The complexity of molecular behaviour has prompted collaborations with other mucineers and especially Tony Corfield, physicists, (sugar) biochemists, microbiologists, optometrists, and clinicians.

Secreted ocular mucin imaged in HEPES buffer with NiCl2. The higher regions of the molecule (here darker blue) are regions of high glycosylation, and at most 1.5 nm above the mica substrate.

Mucin 4 (gift from Kermit Carraway) on graphite, imaged in HEPES buffer with NiCl2 and 0.01% Tween 20.

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