Molecular Arrangement of Cervical Mucus: a Reevaluation Based on Laser Light-Scattering Spectroscopy

Abstract

Evidence obtained from laser light-scattering spectroscopy suggests that the molecular arrangement of cow estrous cervical mucus is an ensemble of entangled random-coiled macromolecules rather than a cross-linked macromolecular network, the model heretofore widely accepted. This new model can account for the following phenomena: The viscoelastic properties of the estrous mucus and human mid-cycle cervical mucus are the result of the way in which the glycoproteins are entangled. Variations of these properties during the reproductive cycle may simply be due to changes in the water content of the cervical mucus. Penetration of spermatozoa in mucus may be entirely mechanical without involving any kind of enzymatic lysis of cross-links (this is supported by changes in the pattern of spermatozoa flagellation during sperm penetration of cervical mucus as shown in motion picture films). The orientation of spermatozoa in the cervical mucus need not be due to the presence of ‘channels’ between micelles but simply to an artifact, the stretching or flow of the mucus, which orients the entangled macromolecules and thus facilitates the penetration of spermatozoa in an axis parallel to them.

Reduced Three-Dimensional Motility in Dehydrated Airway Mucus Prevents Neutrophil Capture and Killing Bacteria on Airway Epithelial Surfaces

“…The gel-forming character of mucus derives mainly from properties of mucin MUC5AC and MUC5B macromolecules, which form a mesh-like entangled network (23,24). To ascertain whether mucus maintained its network structure after manipulation (pipetting, dehydration, dialysis), we stained mucus of three different concentrations with WGA-Rh (Fig.…”

Supramolecular Dynamics of Mucus

“…As pointed out above, results from DLS studies in cow cervical mucus (Lee et al 1977) and in human bronchial mucus sampled by bronchoscopy (Verdugo et al 1983) showed the presence of reptational axial diffusion. These results ruled out the idea that these mucins are held together by interchain covalent bonds (de Gennes and Leger 1982) and provide strong support for the hypothesis that mucus is a physical gel held together by tangles and lowenergy interactions.…”

“…These random movements are reported by two corresponding DSL sets of relaxation times-namely, short relaxation times reflecting limited local lateral polymer mobilities and long relaxation times associated with translational diffusion along the polymer axis that de Gennes and Leger (1982) called "reptation." DSL revealed that both sets of random diffusion mobilities are present in cow estrous cervical mucus (Lee et al 1977) and in human bronchial mucus (Verdugo et al 1983). Because reptation cannot take place in networks held together by covalent cross-links or made out of branched polymers (Edwards and Grant 1973b;de Gennes and Leger 1982;Doi and Edwards 1984), these results provided the first objective indication that the polymer matrix of respiratory and cervical mucus is made of linear mucins that most likely are not chemically cross-linked but are tangled, forming a loosely woven network.…”

“…One of the oldest controversies in mucus research questions the nature of interconnections among mucin chains: whether the mucus is a chemical gel with a matrix containing branched polymers interconnected by covalent S:S bonds, or a physical gel in which linear polymers are held together by tangles and lowenergy electrostatic and hydrophobic bonds (Lee et al 1977;Clamp et al 1978;Verdugo et al 1983). Because the rheological properties of chemical gels depend on the degree of covalent cross-links among polymer chains (Flory 1953), defective control of S:S bonding was thought to be the source of mucus pathology (Clamp et al 1978).…”

“…Among the most critical characteristics of mucins for their role in respiratory mucus is their linear, unbranched conformation. Early work using dynamic laser scattering (DLS) revealed that mucin chains in cervical and respiratory mucus can diffuse along their axis (Lee et al 1977;Verdugo et al 1983). In chemically cross-linked gels, polymers can show only lateral local motion associated to the chain sections between crosslinks (Doi and Edwards 1984).…”