Polymer Gel Phase Transition: The Molecular Mechanism of Product Release in Mucin Secretion?

Abstract

Mucus is a polymer gel resulting from the annealing and hydration of a variety of secretory products. Mucins which are the principal polymeric species in the mucus matrix, are condensed inside secretory granules and undergo massive swelling upon release. Upon exocytosis from goblet cells mucins swell following a typical first order kinetics that is characteristic of polymer gels (Verdugo, 1984; Tanaka and Fillmore, 1979). The swelling of mucus, which is the leading parameter for the control of mucus rheology, is driven by a Donnan potential (Tam and Verdugo, 1981). However the condensation of mucins inside the secretory granule is still not well understood. An important condition for mucin condensation is the shielding of their polyionic charges which depends upon the presence of large amounts of Ca2+ inside the secretory granule (Verdugo et. al., 1987). Although the eationic shield provided by calcium is expected, it is not sufficient to explain a specific molecular mechanism of mucins condensation. We have proposed that the condensation and decondensation of secretory mucins could be explained by a polymer gel phase transition mechanism. The experiments reported here were designed to test if the native polymer network contained in the giant mucin granule of the slugAriolimax columbianus can undergo polymer gel phase transition. Isolated granules were demembranated and suspended in solutions containing different water/glycerol ratios. The volume of the mucin polymer network was monitored by video- microscopy. Video recordings were stored in magnetic tape. Results indicate that the mucin network can expand as much as 600 fold. This volume change is reversible and characteristically discontinuous demonstrating the typical features of a polymer gel phase transition: The critical solvent/non-solvent ratio is 74/26% water/glycerol (pH 7, 20°C), and varies with pH, temperature and Ca2+ concentration.