Mucin Molecules Research Articles

Non-invasive lung disease diagnostics from exhaled microdroplets of lung fluid: perspectives and technical challenges

The combination of ultra-sensitive assay techniques and recent improvements in the instrumentation used to collect microdroplets of lung fluid (MLF) from exhaled breath has enabled the development of non-invasive lung disease diagnostics that are based on MLF analysis. In one example of this approach, electrospun nylon filters were used to collect MLFs from patients with pulmonary tuberculosis. The filters were washed to obtain liquid probes, which were then tested for human immunoglobulin A (h-IgA) and fractions of h-IgA specific to ESAT-6 and Psts-1, two antigens secreted by Mycobacterium tuberculosis. Probes collected for 10 min contained 100–1500 fg of h-IgA and, in patients with pulmonary tuberculosis, a portion of these h-IgA molecules showed specificity to the secreted antigens. Separate MLFs and their dry residues were successfully collected using an electrostatic collector and impactor developed especially for this purpose. Visualization of MLF dry residues by atomic force microscopy made it possible to estimate the lipid content in each MLF and revealed mucin molecules in some MLFs. This exciting new approach will likely make it possible to detect biomarkers in individual MLFs. MLFs emerging from an infection site (‘hot’ microdroplets) are expected to be enriched with infection biomarkers. This paper discusses possible experimental approaches to detecting biomarkers in single MLFs, as well as certain technological problems that need to be resolved in order to develop new non-invasive diagnostics based on analysing biomarkers in separate MLFs.

Mucoadhesive functionality of cell wall structures from fruits and grains: Electrostatic and polymer network interactions mediated by soluble dietary polysaccharides

We demonstrate the enhancement of intestinal mucin (Muc2) binding to plant cell wall structures from fruit (parenchymal apple tissue) and grain (wheat endosperm) mediated by soluble dietary fibers embedded within cellulose networks. Mucin binding occurs through two distinct mechanisms; for pectin polysaccharides characteristic of fruits and vegetables, it is governed by molecular mucoadhesive interactions, while for neutral polysaccharides, arabinoxylan and β-glucan characteristic of cereal grains, the interaction stems from the properties of their polymer network. Based on microrheological and microscopic measurements, we show that neutral dietary fiber polysaccharides do not adhere to intestinal mucin, but are capable of disrupting the mucin network, which facilitates interpenetration of mucin molecules into the polysaccharide mesh. This effect becomes significant in the context of ‘whole foods’, where soluble fibers are incorporated within the gel-like matrix of cellulose-reinforced plant cell wall structures. The result of mucoadhesion assay and analysis of microscopy images points to the critical role of entanglements between mucin and polysaccharides as a lock-in mechanism preventing larger mucin from escaping out of plant cell wall structures. These results provide the first indication that non-pectin soluble dietary fiber may influence mucosal interactions, mucus barrier properties, and transmucosal transport of nutrients.

Age-dependent capillary thinning dynamics of physically-associated salivary mucin networks

Human whole saliva consists of a physically-associated network of mucin molecules. The interchain physical associations control the rheological characteristics of the solution and in particular, the lifetime of filaments and threads. Measurements show that the shear rheology of salivary mucin solutions (as measured by steady shear viscosity and small amplitude oscillatory shear) is quite insensitive to sample age over a 24 h period following sample collection. By contrast, the filament thinning dynamics vary dramatically, with the characteristic relaxation time of the saliva and the breakup time of a fluid thread decreasing significantly with sample age. We interpret our results within the framework of a sticky finitely extensible network model which respects the known physical dimensions and properties of the mucin molecules in saliva and models them as a network of physically associating and finitely extensible polymer chains. The model predicts an initially strain-hardening response in the transient ex...

The role of mucus on drug transport and its potential to affect therapeutic outcomes.

A layer of mucus covers the surface of all wet epithelia throughout the human body. Mucus is a hydrogel mainly composed of water, mucins (glycoproteins), DNA, proteins, lipids, and cell debris. This complex composition yields a tenacious viscoelastic hydrogel that lubricates and protects the exposed epithelia from external threats and enzymatic degradation. The natural protective role of mucus is nowadays acknowledged as a major barrier to be overcome in non-invasive drug delivery. The heterogeneity of mucus components offers a wide range of potential chemical interaction sites for macromolecules, while the mesh-like architecture given to mucus by the intermolecular cross-linking of mucin molecules results in a dense network that physically, and in a size-dependent manner, hinders the diffusion of nanoparticles through mucus. Consequently, drug diffusion, epithelial absorption, drug bioavailability, and ultimately therapeutic outcomes of mucosal drug delivery can be attenuated.

Innate immune defense in the inner ear - mucines are expressed by the human endolymphatic sac.

The human endolymphatic sac has been shown recently to have immunological capacities and has thus been proposed as the main entity protecting the inner ear from pathogen invasion, equivalent to mucosa-associated lymphoid tissue (MALT). Although the sac expresses molecules of the innate immune system, the potential expression of members of the important mucin family has not been detailed. Thus, this paper explores endolymphatic sac expression of a number of mucins and mucin precursors. Twelve fresh tissue samples from the human endolymphatic sac were obtained during translabyrinthine surgery. The expression of Mucin 1, 2, 5B/AC and 16, as well as the core structure elements (mucin precursors) T-antigen, Tn-antigen and Sialyl-Tn-antigen was investigated by immunohistochemistry. The endolymphatic sac epithelium expressed MUC1 (both apically towards the endolymphatic sac (ES) lumen and basally towards the capillary network), MUC 16 and Tn-antigen. There was no labeling after incubation with antibodies against T-antigen, sialyl-Tn-antigen, MUC2 and MUC5B/AC. We conclude that the human endolymphatic sac epithelium expresses a number of mucin molecules, which supports the hypothesis of the sac as the primary immunological tissue structure of the inner ear, equivalent to MALT in other organs. The mucins may also play a role in the formation and continuous homeostasis of the inner ear fluids, as well as the pathogenesis of Meniere's disease.

Characterization of mucin – lipid droplet interactions: Influence on potential fate of fish oil-in-water emulsions under simulated gastrointestinal conditions

The influence of mucin upon the properties and stability of oil-in-water emulsions containing lipid droplets coated by either a protein (caseinate) or non-ionic surfactant (Tween 80) was studied. At pH values below the isoelectric point of emulsion (e.g., stomach conditions), anionic mucin molecules bound to the surfaces of cationic caseinate-coated lipid droplets, which led to extensive bridging flocculation and droplet coalescence. Conversely, at pH values above the isoelectric point (e.g., mouth conditions), there was an electrostatic repulsion between anionic mucin molecules and anionic caseinate-coated lipid droplets. At this pH, relatively high levels of mucin promoted droplet flocculation through a depletion mechanism. The extent of droplet flocculation and/or coalescence in the systems depended on both the droplet and mucin concentration. Emulsions stabilized by the non-ionic surfactant were not susceptible to bridging flocculation, and only exhibited depletion flocculation at high mucin levels, which was attributed to the strong steric repulsion between them. These results have important implications for understanding the gastrointestinal fate of lipid droplets, which is critical for the development of foods with improved nutritional attributes.

Molecular Structure and Equilibrium Forces of Bovine Submaxillary Mucin Adsorbed at a Solid-Liquid Interface.

By combining dynamic light scattering, circular dichroism spectroscopy, atomic force microscopy, and surface force apparatus, the conformation of bovine submaxillary mucin in dilute solution and nanomechanical properties of mucin layers adsorbed on mica have been investigated. The samples were prepared by additional chromatographic purification of commercially available products. The mucin molecule was found to have a z-average hydrodynamic diameter of ca. 35 nm in phosphate buffered solution, without any particular secondary or tertiary structure. The contour length of the mucin is larger than, yet of the same order of magnitude as the diameter, indicating that the molecule can be modeled as a relatively rigid polymeric chain due to the large persistence length of the central glycosylated domain. Mucin molecules adsorbed abundantly onto mica from saline buffer, generating polymer-like, long-ranged, repulsive, and nonhysteretic forces upon compression of the adsorbed layers. Detailed analysis of such forces suggests that adsorbed mucins had an elongated conformation favored by the stiffness of the central domain. Acidification of aqueous media was chosen as means to reduce mucin-mucin and mucin-substrate electrostatic interactions. The hydrodynamic diameter in solution did not significantly change when the pH was lowered, showing that the large persistence length of the mucin molecule is due to steric hindrance between sugar chains, rather than electrostatic interactions. Remarkably, the force generated by an adsorbed layer with a fixed surface coverage also remained unaltered upon acidification. This observation can be linked to the surface-protective, pH-resistant role of bovine submaxillary mucin in the variable environmental conditions of the oral cavity.

Electrochemical behaviour of a cobalt-chromium-molybdenum dental alloy in artificial salivas:Influence of phosphate ions and mucin components.

The stability of the Co-Cr-Mo dental alloy immersed in artificial salivas (pH 6.7) was investigated over 24 h. Three artificial salivas have been studied: saline saliva (saliva I); saline saliva buffered with phosphate ions (saliva II) and saliva II plus mucin molecules (saliva III). For all the systems, open circuit potential shift positively over 24 hours of immersion. Data extracted from the steady-state polarization curves demonstrated that the Co-Cr-Mo alloy has higher corrosion potential in saliva III, lower corrosion potential in saliva I and lower initial corrosion resistance in saliva III. After 24 hours of immersion in the artificial salivas, the Co-Cr-Mo alloy presents high corrosion stability, due to the protective action created by the presence of corrosion products. From the analysis of the breakdown potential it was concluded that, the presence of the phosphate ions and mucin promote the oxidation process, inducing the formation of etch pits. Regarding the effect of the mucin concentration in the corrosion behaviour of the Co-Cr-Mo dental alloy, it was observed a negative shift in the corrosion potential, pointing to a cathodic inhibitor role for the mucin molecules. Nevertheless, no correlation between the mucin concentration and corrosion rate was possible to establish.

Carbachol-induced colonic mucus formation requires transport via NKCC1, K⁺ channels and CFTR.

The colonic mucosa protects itself from the luminal content by secreting mucus that keeps the bacteria at a distance from the epithelium. For this barrier to be effective, the mucus has to be constantly replenished which involves exocytosis and expansion of the secreted mucins. Mechanisms involved in regulation of mucus exocytosis and expansion are poorly understood, and the aim of this study was to investigate whether epithelial anion secretion regulates mucus formation in the colon. The muscarinic agonist carbachol was used to induce parallel secretion of anions and mucus, and by using established inhibitors of ion transport, we studied how inhibition of epithelial transport affected mucus formation in mouse colon. Anion secretion and mucin exocytosis were measured by changes in membrane current and epithelial capacitance, respectively. Mucus thickness measurements were used to determine the carbachol effect on mucus growth. The results showed that the carbachol-induced increase in membrane current was dependent on NKCC1 co-transport, basolateral K(+) channels and Cftr activity. In contrast, the carbachol-induced increase in capacitance was partially dependent on NKCC1 and K(+) channel activity, but did not require Cftr activity. Carbachol also induced an increase in mucus thickness that was inhibited by the NKCC1 blocker bumetanide. However, mice that lacked a functional Cftr channel did not respond to carbachol with an increase in mucus thickness, suggesting that carbachol-induced mucin expansion requires Cftr channel activity. In conclusion, these findings suggest that colonic epithelial transport regulates mucus formation by affecting both exocytosis and expansion of the mucin molecules.

Flagellin modulates TIM4 expression in mast cells.

T-helper (Th) 2 polarization functions in a number of immune diseases, but their pathogenesis needs further investigation. Some microbial products or components are strong adjuvants in the creation of mouse models of Th2 polarization. T cell immunoglobulin mucin molecule (TIM) 4 is a facilitator in the initiation of Th2 response. This study looks at the role of one of the microbial products, flagellin (FGN), in the induction of TIM4 expression in mast cells. Bone marrow derived mast cells (BMMC) were generated. Induction of TIM4 in mast cells was assessed in both experiments in vitro and in vivo. The signal transducer and activator of transcription 6 (Stat6) phosphorylation in BMMC were assessed by Western blotting. A coculture model with FGN-primed BMMC and naïve CD4(+) T cells was employed to assess FGN in facilitating the expression of TIM4 in mast cells. After exposure to FGN, TIM4 levels were significantly increased in BMMC and mast cells of the mouse intestine, which was accompanied by increased STAT6 phosphorylation. Culture with FGN-primed BMMC, naïve CD4(+) T cells developed into Th2 cells by a TIM4-dependent manner. We conclude that FGN can induce mast cells to express TIM4, which helps initiate Th2 polarization.

Extremely Soft: Design with Rheologically Complex Fluids

Abstract Soft is a relative term. Its scope includes the extreme of viscoelastic materials that exhibit both liquid-like and solid-like properties depending on loading conditions. Such rheologically complex materials are abundant in biological organisms, including mucin gels, blood, cellular cytoplasm, and molecules of protein or DNA. However, comparably soft, rheologically complex materials are not yet in the standard toolbox of the engineer. Engineering design generally, and robotic design specifically, stand to benefit greatly from soft and rheologically complex materials that could offer novel performance based on nonlinear material properties. In order to achieve this, several technical challenges must be overcome, including better conceptual modeling, more predictive mathematical modeling, and an overall design framework that manages the high dimensionality of rheological material properties. This article outlines the challenges, and as a first step toward overcoming them, describes a design process...

Emerging Role of Mucins in Epithelial to Mesenchymal Transition

Epithelial to mesenchymal transition (EMT) is an important and complex phenomenon that determines the aggressiveness of cancer cells. The morphological transformation of cancerous cells is accompanied by various cellular processes such as alterations in cell-cell adhesion, cell matrix degradation, down regulation of epithelial marker Ecadherin and upregulation of mesenchymal markers N-cadherin and Vimentin. Besides these markers several other important tumor antigens/mucins are also involved in the EMT process. Mainly high molecular weight glycoproteins such as mucin molecules (MUC1, MUC4 and MUC16) play a major role in the cellular transformation and signaling alteration in EMT process. In addition to these factors, EMT may be an essential process triggering the emergence or expansion of the CSC population, which slowly results in the initiation of tumor at metastatic sites. Furthermore, mucins have been demonstrated to be involved in the EMT process and also in the enrichment of cancer stem cell population. Mucin mediated EMT is very complex since the key components of tumor microenvironment are also regulating mucin molecules. In this review, we have discussed all the aforementioned factors and their mechanistic involvement for EMT process.

High MUC2 Expression in Ovarian Cancer Is Inversely Associated with the M1/M2 Ratio of Tumor-Associated Macrophages and Patient Survival Time

Mucin 2 (MUC2) is a mucin molecule aberrantly expressed by ovarian cancer cells. Previous in vitro studies have indicated that MUC2 promotes cancer growth and metastasis through a tumor-associated macrophage (TAM)-dependent mechanism. However, this mechanism has never been linked to clinical oncology, and its prognostic significance needed to be clarified. Here, we collected 102 consecutive ovarian cancer specimens and used the multiple immuno-histo-chemical/-fluorescent technique to determine the correlations between the MUC2 expression status, the ratio of M1/M2 TAMs and the densities of cyclooxygenase-2 (COX-2)+ TAMs and COX-2+ cancer cells. The Kaplan-Meier survival analysis and multivariate Cox regression analysis were used to evaluate the prognostic influences of these parameters. As a result, we found that the MUC2 overexpression (immunostaining ++/+++) was significantly correlated with a reduced ratio of M1/M2 TAMs (p<0.001), an increased density of COX-2+ TAMs (p<0.001) and an increased density of COX-2+ cancer cells (p=0.017). Moreover, most of the M2 TAMs (93%-100%) and COX-2+ TAMs (63%-89%) overlapped; and the COX-2+ cancer cells were frequently observed near the COX-2+ TAMs. In the Cox regression analysis, MUC2 overexpression was found to be an independent prognostic factor for ovarian cancer patients, of which the hazard ratio (HR) was 2.354 (95% confidence interval (CI): 1.031-10.707, p=0.005). Also, the reduced ratio of M1/M2 TAMs and the increased densities of COX-2+ TAMs and COX-2+ cancer cells were demonstrated to be the predictors of poor prognosis, among which the reduced M1/M2 ratio possessed the highest HR (1.767, 95% CI: 1.061-6.957, p=0.019). All these findings revealed that MUC2 can concurrently exert M2-polarizing and COX-2-inducing effects on TAMs, by which it causes an imbalanced TAM M1-/M2-polarization pattern and induces local PGE2 synthesis (in both TAMs and cancer cells). The positive feedback between local PGE2 synthesis and TAM M2-polarization accelerates ovarian cancer progression.

TIM-family molecules in embryonic hematopoiesis: Fetal liver TIM-4lo cells have myeloid potential

Trans-membrane (or T cell) immunoglobulin and mucin (TIM) molecules are known regulators of immune response whose function in hematopoiesis is unknown. Earlier, we found that tim-1 and tim-4 are expressed by CD45(+) cells in the para-aortic region of chicken embryo. Because the para-aortic region is a known site for hematopoietic stem cell (HSC) and hematopoietic progenitor cell (HPC) differentiation and expansion, we hypothesize that TIM molecules have a role in hematopoiesis. To study this role further, we analyzed TIM expression more precisely in chicken para-aortic region and mouse fetal liver hematopoietic cells. Additionally, we examined the hematopoietic potential of TIM-4(+) mouse fetal liver cells with a colony-forming assay. tim-1 gene expression was detected in chicken and mouse embryos in the aorta-gonads-mesonephros-region at the time of HSC emergence, whereas tim-3 mRNA was widely expressed in different tissues. tim-4 expression was restricted to fetal liver CD45(+)F4/80(+) cells. Moreover, two TIM-4(+) populations were distinguished: F4/80(hi)TIM-4(hi) and F4/80(lo)TIM-4(lo). F4/80(hi)TIM-4(hi) cells had no hematopoietic potential and were morphologically similar to mature macrophages, suggesting that they are yolk sac-derived macrophages. Instead, many of the F4/80(lo)TIM-4(lo) cells were c-kit(+) and Sca-1(+) and had primitive morphology and multilineage colony-forming ability. In addition, F4/80(lo)TIM-4(lo) cells included a considerable population expressing ER-MP12, a known marker for macrophage colony-forming cells and other myeloid progenitors. We conclude that TIM molecules are expressed in embryonic hematopoietic tissues in chicken and mouse and that in fetal liver, TIM-4 is expressed by myeloid progenitor cells.

Carbohydrate Determinants in Ferret Conjunctiva are Affected by Infection with Influenza H1N1 Virus

Background: Carbohydrates often accomplish as cell-surface receptors for microorganisms and influenza virus preferentially binds to sialic acid through the viral haemagglutinin. The virus may attach not only to the epithelium in the airways, but also to the surface ocular epithelium.Purpose: To decide if ferrets can be used to study virus induced conjunctivitis and to evaluate changes in the conjunctival glycosylation pattern during an influenza attack.Methods: Ferrets were infected with H1N1 influenza virus via nasal inoculation. The in situ carbohydrate expressions in eyelid sections from ferrets 0 to 10 days after infection was examined using lectin- and immunohistochemistry.Results: The conjunctival cells became hypertrophic with appearance of both PAS positive and PAS + Alcian Blue stained cells 5–6 days after inoculation. The binding of three sialic acid detecting lectins were investigated: WGA, MAA2 and SNA1. While none of them stained conjunctival epithelial cells in the non-infected ferrets to any extent, there was a positive conjunctival reaction in the infected ferret after incubation with all three lectins. Binding of a MUC1 antibody that seems to detect sialylated determinants in the mucin molecule indicates that MUC1 is de novo expressed in most of the squamous conjunctival cells at the start of the influenza infection. MUC5AC positive epithelial cells, probably goblet cells, proliferate in the diseased conjunctiva.Conclusion: Nasal inoculation of H1N1 virus to ferrets has an effect on the conjunctival cells and change their expression of glycans. Synthesized glycans are an integral part of the tear film and the present study contributes to reveal the changes that occur in the surface epithelium in the eyelid and thereby to elucidate the pathophysiology of the virus mediated conjunctivitis. Ferrets are suitable animal models to study human conjunctivitis mediated by human influenza virus.

Chemical modification of carbohydrates in tissue sections may unmask mucin antigens

Expression of mucins in cells and tissues is of great diagnostic and prognostic importance, and immunohistochemistry frequently is used to detect them. Reports concerning mucin localization in sections sometimes are conflicting, however, partly because immunogenic regions of the mucin molecule may be masked and thus not available for binding to an antibody. We modified carbohydrates in tissue sections chemically to enhance the binding of monoclonal mucin antibodies and of the lectin, Vicia villosa B4, to human tissue. The immunohistochemical localization of MUC1 and the simple mucin-type antigens, Tn and sialyl-Tn, was influenced by oxidation with periodic acid and by β-elimination before incubation. In some epithelial cells the staining was prevented by these procedures while in other cells it was evident. It appears that chemical modification can either destroy some antigen binding sites or unmask cryptic antigen binding sites in the mucin molecule and thereby make them accessible for immunohistochemical detection.

Improved Cellular Specificity of Plasmonic Nanobubbles versus Nanoparticles in Heterogeneous Cell Systems

The limited specificity of nanoparticle (NP) uptake by target cells associated with a disease is one of the principal challenges of nanomedicine. Using the threshold mechanism of plasmonic nanobubble (PNB) generation and enhanced accumulation and clustering of gold nanoparticles in target cells, we increased the specificity of PNB generation and detection in target versus non-target cells by more than one order of magnitude compared to the specificity of NP uptake by the same cells. This improved cellular specificity of PNBs was demonstrated in six different cell models representing diverse molecular targets such as epidermal growth factor receptor, CD3 receptor, prostate specific membrane antigen and mucin molecule MUC1. Thus PNBs may be a universal method and nano-agent that overcome the problem of non-specific uptake of NPs by non-target cells and improve the specificity of NP-based diagnostics, therapeutics and theranostics at the cell level.

Construction of a Natural Mucin Microarray and Interrogation for Biologically Relevant Glyco-Epitopes

Mucins are the principal components of mucus, and mucin glycosylation has important roles in defense, microbial adhesion, immunomodulation, inflammation, and cancer. Mucin expression and glycosylation are dynamic, responding to changes in local environment and disease. Potentially hundreds of heterogeneous glycans can substitute one mucin molecule, and it is difficult to identify biologically accessible glyco-epitopes. Thirty-seven mucins, from the reproductive and gastrointestinal (GI) tracts of six species (bovine, ovine, equine, porcine, chicken, and deer) and from two human-derived cell lines, were purified. Following optimization of mucin printing and construction of a novel mucin microarray, the glycoprofiles of the whole mucins on the microarray were compared using a panel of lectins and one antibody. Accessible glyco-motifs of GI mucins varied according to species and localization of mucin origin, with terminal fucose, the sialyl T-antigen, and N-linked oligosaccharides identified as potentially important. The occurrence of T- and sialyl T-antigen varied in bovine and ovine reproductive tract mucins, and terminal N-acetylgalactosamine (GalNAc) and sulfated carbohydrates were detected. This study introduces natural mucin microarrays as an effective tool for profiling mucin glyco-epitopes and highlights their potential for discovery of biologically important motifs in bacterial-host interactions and fertility.

Rejection and regulation

Achieving allograft tolerance is the holy grail of transplantation. However, tolerance and rejection are two extreme ends of a scale that can be tipped in either direction. We review the novel effector and regulatory mechanisms involved and factors that tip the balance in favor of rejection or regulation. It is increasingly recognized that established T-cell phenotypes could change their commitments. New data point to the plasticity of Th17 cells in vivo with a reciprocal balance of Th17 cells and regulatory T cells (Tregs) driven by the local cytokine environment. Treg-cell profiles have been linked to acute and chronic allograft outcomes, and emerging data also indicate a novel role of a regulatory B-cell population. Current research efforts are looking into factors that tip the balance toward allograft tolerance by targeting cytokines, novel costimulatory pathways such as T-cell immunoglobulin mucin molecules, and components of innate immunity, particularly dendritic cells. The balance of effector and regulatory mechanisms contributing to allograft outcome is very complex. It is likely that targeting multiple pathways will be required to achieve tolerance. Further studies are warranted to define this balance and identify optimal combination of therapeutic interventions.

Distribution of Sialic Acids on Mucins and Gels: A Defense Mechanism

Moist mucosal epithelial interfaces that are exposed to external environments are dominated by sugar epitopes, some of which (e.g., sialic acids) are involved in host defense. In this study, we determined the abundance and distribution of two sialic acids to assess differences in their availability to an exogenous probe in isolated mucins and mucous gels. We used atomic force microscopy to obtain force maps of human preocular mucous and purified ocular mucins by probing and locating the interactions between tip-tethered lectins Maackia amurensis and Sambucus nigra and their respective receptors, α-2,3 and α-2,6 N-acetylneuraminic (sialic) acids. The rupture force distributions were not affected by neighboring sugar-bearing molecules. Energy contours for both lectin-sugar bonds were fitted to a two-barrier model, suggesting a conformational change before dissociation. In contrast to data from purified mucin molecules, the preocular gels presented numerous large clusters (19,000 ± 4000 nm2) of α-2,6 sialic acids, but very few small clusters (2000 ± 500 nm2) of α-2,3 epitopes. This indicates that mucins, which are rich in α-2,3 sialic acids, are only partially exposed at the surface of the mucous gel. Microorganisms that recognize α-2,3 sialic acids will encounter only isolated ligands, and the adhesion of other microorganisms will be enhanced by large islands of neighboring α-2,6 sialic acids. We have unveiled an additional level of mucosal surface heterogeneity, specifically in the distribution of pro- and antiadhesive sialic acids that protect underlying epithelia from viruses and bacteria.