Mucus Viscoelasticity Research Articles

Dysregulated Airway Host Defense in Hyper IgE Syndrome due to STAT3 Mutations.

Hyper IgE syndrome (STAT3-HIES), also known as Job's syndrome, is a rare immunodeficiency disease typically caused by dominant-negative STAT3 mutations. STAT3-HIES syndrome is characterized by chronic pulmonary infection and inflammation, suggesting impairment of pulmonary innate host defense. To identify airway epithelial host defense defects consequent to STAT3 mutations that, in addition to reported mutant STAT3 immunologic abnormalities, produce pulmonary infection. STAT3-HIES sputum was evaluated for biochemical/biophysical properties. STAT3-HIES excised lungs were harvested for histology; bronchial brush samples were collected for RNA sequencing and in vitro culture. A STAT3-HIES-specific mutation (R382W), expressed by lentiviruses, and a STAT3 knockout, generated by CRISPR/Cas9, were maintained in normal human bronchial epithelia under basal or inflammatory (IL1β) conditions. Effects of STAT3 deficiency on transcriptomics, and epithelial ion channel, secretory, antimicrobial, and ciliary functions were assessed. Mucus concentrations and viscoelasticity were increased in STAT3-HIES sputum. STAT3-HIES excised lungs exhibited mucus obstruction and elevated IL1β expression. STAT3 deficiency impaired CFTR-dependent fluid and mucin secretion, inhibited expression of antimicrobial peptides, cytokines, and chemokines, and acidified airway surface liquid at baseline and post-IL1β exposure in vitro. Notably, mutant STAT3 suppressed IL1R1 expression. STAT3 mutations also inhibited ciliogenesis in vivo and impaired mucociliary transport in vitro, a process mediated via HES6 suppression. Administration of a γ-secretase inhibitor increased HES6 expression and improved ciliogenesis in STAT3 R382W mutant cells. STAT3 dysfunction leads to multi-component defects in airway epithelial innate defense, which, in conjunction with STAT3-HIES immune deficiency, contributes to chronic pulmonary infection.

Heat and concentration analysis of two-layered muco-ciliary third grade fluid flow in human airways

Understanding the mechanisms involved in the movement and clearance of mucus within the human airways is important from a physiological perspective. A mathematical model of muco-ciliary two-layered fluid flow in a finite two-dimensional channel is proposed. Due to the presence of both the airway ciliary layer (ACL) and the periciliary liquid layer (PCL) in airways epithelial cells, the two-layered model is adopted. The third grade fluid models is used to characterize the viscoelastic nature of mucus secreted in the airways. The mathematical modeling of two-layer flow problem is simplified by using long wavelength and small Reynolds number approximation. A formulated set of partial differential equations (PDEs) is solved for series-form solutions of velocity, temperature, concentration, and pressure gradient by using the Adomian decomposition method (ADM). The analysis delineated that with an increase in pressure gradient at airways entrance ξ the velocity and temperature increases while concentration decreases. Deborah numbers impact ACL and PCL velocities differently, with De(A) influencing flow direction and De(P) causing fluid to flow faster in the forward direction. It also emphasizes the significance of the rate of thermal diffusion, viscous dissipation, and relaxation time. The results showed that the suggested two-layered muco-ciliary model provides a better description of mucus transport in the human airways. The pressure gradient at the airways entrance has a significant impact on mucus transport through the airways.

Viscoelastic characterization of the mucus from the skin of loach (II) using linear viscoelastic property

ABSTRACT A structuralized Rivlin-Sawyers model with inhomogeneous shear-rate effect on the component of relaxation spectrum was proposed here to express the viscoelastic property of loach mucus. The linear viscoelastic property of the mucus was obtained using the experimental frequency sweep data at small strain, and the viscosity in the shear-rate decreasing region with 0.0631 s−1 as the maximum shear rate was fitted by the model with inhomogeneous shear-rate effect. Both the predictions of the steady viscosity curves with four maximum shear rates, i.e., 0.004 s−1, 0.01 s−1, 0.1 s−1, and 1 s−1, and that of the transient shear viscosity in the step rate experiment at 0.1 s−1 show reasonable characterization of the model on the viscoelasticity of the loach skin mucus.

Thiolated polyglycerol sulfate as potential mucolytic for muco-obstructive lung diseases.

Increased disulfide crosslinking of secreted mucins causes elevated viscoelasticity of mucus and is a key determinant of mucus dysfunction in patients with cystic fibrosis (CF) and other muco-obstructive lung diseases. In this study, we describe the synthesis of a novel thiol-containing, sulfated dendritic polyglycerol (dPGS-SH), designed to chemically reduce these abnormal crosslinks, which we demonstrate with mucolytic activity assays in sputum from patients with CF. This mucolytic polymer, which is based on a reportedly anti-inflammatory polysulfate scaffold, additionally carries multiple thiol groups for mucolytic activity and can be produced on a gram-scale. After a physicochemical compound characterization, we compare the mucolytic activity of dPGS-SH to the clinically approved N-acetylcysteine (NAC) using western blot studies and investigate the effect of dPGS-SH on the viscoelastic properties of sputum samples from CF patients by oscillatory rheology. We show that dPGS-SH is more effective than NAC in reducing multimer intensity of the secreted mucins MUC5B and MUC5AC and demonstrate significant mucolytic activity by rheology. In addition, we provide data for dPGS-SH demonstrating a high compound stability, low cytotoxicity, and superior reaction kinetics over NAC at different pH levels. Our data support further development of the novel reducing polymer system dPGS-SH as a potential mucolytic to improve mucus function and clearance in patients with CF as well as other muco-obstructive lung diseases.

350 Cervical mucus viscoelasticity and sperm velocity are correlated and concentration dependent in vitro

350 Cervical mucus viscoelasticity and sperm velocity are correlated and concentration dependent in vitro

On the role of viscoelasticity in mucociliary clearance: a hydrodynamic continuum approach

We present numerical and analytical predictions of mucociliary clearance based on the continuum description of a viscoelastic mucus film, where momentum transfer from the beating cilia is represented via a Navier-slip boundary condition introduced by Bottier et al. (PLoS Comput. Biol., vol. 13, issue 7, 2017a, e1005552). Mucus viscoelasticity is represented via the Oldroyd-B model, where the relaxation time and the viscosity ratio have been fitted to experimental data for the storage and loss moduli of different types of real mucus, ranging from healthy to diseased conditions. We solve numerically the fully nonlinear governing equations for inertialess flow, and develop analytical solutions via asymptotic expansion in two limits: (i) weak viscoelasticity, i.e. low Deborah number; (ii) low cilia beat amplitude (CBA). All our approaches predict a drop in the mucus flow rate in relation to the Newtonian reference value, as the cilia beat frequency is increased. This relative drop increases with decreasing CBA and slip length. In diseased conditions, e.g. mucus properties characteristic of cystic fibrosis, the drop reaches 30 % in the physiological frequency range. In the case of healthy mucus, no significant drop is observed, even at very high frequency. This contrasts with the deterioration of microorganism propulsion predicted by the low-amplitude theory of Lauga (Phys. Fluids, vol. 19, issue 8, 2007, 083104), and is due to the larger beat amplitude and slip length associated with mucociliary clearance. In the physiological range of the cilia beat frequency, the low-amplitude prediction is accurate for both healthy and diseased conditions. Finally, we find that shear-thinning, modelled via a multi-mode Giesekus model, does not significantly alter our weakly viscoelastic and low-amplitude predictions based on the Oldroyd-B model.

Altering the viscoelastic properties of mucus-grown Pseudomonas aeruginosa biofilms affects antibiotic susceptibility

The viscoelastic properties of biofilms are correlated with their susceptibility to mechanical and chemical stress, and the airway environment in muco-obstructive pulmonary diseases (MOPD) facilitates robust biofilm formation. Hyperconcentrated, viscoelastic mucus promotes chronic inflammation and infection, resulting in increased mucin and DNA concentrations. The viscoelastic properties of biofilms are regulated by biopolymers, including polysaccharides and DNA, and influence responses to antibiotics and phagocytosis. We hypothesize that targeted modulation of biofilm rheology will compromise structural integrity and increase antibiotic susceptibility and mucociliary transport. We evaluate biofilm rheology on the macro, micro, and nano scale as a function of treatment with a reducing agent, a biopolymer, and/or tobramycin to define the relationship between the viscoelastic properties of biofilms and susceptibility. Disruption of the biofilm architecture is associated with altered macroscopic and microscopic moduli, rapid vector permeability, increased antibiotic susceptibility, and improved mucociliary transport, suggesting that biofilm modulating therapeutics will improve the treatment of chronic respiratory infections in MOPD.

Synthetic mucus for an ex vivo phonation setup: Creation, application, and effect on excised porcine larynges.

Laryngeal mucus hydrates and lubricates the deformable tissue of the vocal folds and acts as a boundary layer with the airflow from the lungs. However, the effects of the mucus' viscoelasticity on phonation remain widely unknown and mucus has not yet been established in experimental procedures of voice research. In this study, four synthetic mucus samples were created on the basis of xanthan with focus on physiological frequency-dependent viscoelastic properties, which cover viscosities and elasticities over 2 orders of magnitude. An established ex vivo experimental setup was expanded by a reproducible and controllable application method of synthetic mucus. The application method and the suitability of the synthetic mucus samples were successfully verified by fluorescence evidence on the vocal folds even after oscillation experiments. Subsequently, the impact of mucus viscoelasticity on the oscillatory dynamics of the vocal folds, the subglottal pressure, and acoustic signal was investigated with 24 porcine larynges (2304 datasets). Despite the large differences of viscoelasticity, the phonatory characteristics remained stable with only minor statistically significant differences. Overall, this study increased the level of realism in the experimental setup for replication of the phonatory process enabling further research on pathological mucus and exploration of therapeutic options.

Surface Engineering of Protein Nanoparticles Modulates Transport, Adsorption, and Uptake in Mucus.

Protein nanoparticles have been demonstrated as effective carriers for protein antigens and therapeutics due to properties endowed by their protein composition. They exhibit high protein to carrier yields, biocompatibility, and heterogeneous surface properties. While protein nanoparticles have been delivered via multiple routes, including intranasal, their interactions with mucosal barriers have not been well studied or modified. Biological barriers associated with intranasal delivery consist of viscoelastic mucus that hinders material transport through surface interactions and the underlying epithelium. Herein, we altered protein nanoparticle surface properties and characterized interactions with nasal mucus and the subsequent effects on diffusion, cellular uptake, and immune cell maturation. Ovalbumin protein nanoparticles were used, serving as a model vaccine nanoparticle. Unmodified ovalbumin protein nanoparticles were compared to cationic ovalbumin particles functionalized with amine groups, neutral particles functionalized with polyethylene glycol, and zwitterionic particles coated layer-by-layer (LBL) with chitosan and oligonucleotides. Transport analysis indicated rapid diffusion of polyethylene glycol and LBL-modified ovalbumin nanoparticles in porcine nasal mucus, while cationic particles were mucoadhesive. Cellular uptake in the presence of mucus by epithelial and dendritic cells was highest for particles containing positive charges, both LBL and amine-functionalized. These particles also exhibited the most diverse adsorbed protein corona from nasal fluids. The corona impacted both dendritic cell uptake and maturation, with polyethylene glycol and LBL modifications improving CD86 expression. Altogether, surface modifications on protein-based nanocarriers are shown to facilitate distinctive physical and cellular behavior associated with mucosal delivery.

The ulcerative colitis-associated gene FUT8 regulates the quantity and quality of secreted mucins

Mucins are the main macrocomponents of the mucus layer that protects the digestive tract from pathogens. Fucosylation of mucins increases mucus viscoelasticity and its resistance to shear stress. These properties are altered in patients with ulcerative colitis (UC), which is marked by a chronic inflammation of the distal part of the colon. Here, we show that levels of Fucosyltransferase 8 (FUT8) and specific mucins are increased in the distal inflamed colon of UC patients. Recapitulating this FUT8 overexpression in mucin-producing HT29-18N2 colonic cell line increases delivery of MUC1 to the plasma membrane and extracellular release of MUC2 and MUC5AC. Mucins secreted by FUT8 overexpressing cells are more resistant to removal from the cell surface than mucins secreted by FUT8-depleted cells (FUT8 KD). FUT8 KD causes intracellular accumulation of MUC1 and alters the ratio of secreted MUC2 to MUC5AC. These data fit well with the Fut8-/- mice phenotype, which are protected from UC. Fut8-/- mice exhibit a thinner proximal colon mucus layer with an altered ratio of neutral to acidic mucins. Together, our data reveal that FUT8 modifies the biophysical properties of mucus by controlling levels of cell surface MUC1 and quantity and quality of secreted MUC2 and MUC5AC. We suggest that these changes in mucus viscoelasticity likely facilitate bacterial-epithelial interactions leading to inflammation and UC progression.

Effects of Mucin and DNA Concentrations in Airway Mucus on Pseudomonas aeruginosa Biofilm Recalcitrance.

ABSTRACTThe pathological properties of airway mucus in cystic fibrosis (CF) are dictated by mucus concentration and composition, with mucins and DNA being responsible for mucus viscoelastic properties. As CF pulmonary disease progresses, the concentrations of mucins and DNA increase and are associated with increased mucus viscoelasticity and decreased transport. Similarly, the biophysical properties of bacterial biofilms are heavily influenced by the composition of their extracellular polymeric substances (EPS). While the roles of polymer concentration and composition in mucus and biofilm mechanical properties have been evaluated independently, the relationship between mucus concentration and composition and the biophysical properties of biofilms grown therein remains unknown. Pseudomonas aeruginosa biofilms were grown in airway mucus as a function of overall concentration and DNA concentration to mimic healthy, and CF pathophysiology and biophysical properties were evaluated with macro- and microrheology. Biofilms were also characterized after exposure to DNase or DTT to examine the effects of DNA and mucin degradation, respectively. Identifying critical targets in biofilms for disrupting mechanical stability in highly concentrated mucus may lead to the development of efficacious biofilm therapies and ultimately improve CF patient outcomes. Overall mucus concentration was the predominant contributor to biofilm viscoelasticity and both DNA degradation and mucin reduction resulted in compromised biofilm mechanical strength.IMPORTANCE Pathological mucus in cystic fibrosis (CF) is highly concentrated and insufficiently cleared from the airway, causing chronic inflammation and infection. Pseudomonas aeruginosa establishes chronic infection in the form of biofilms within mucus, and this study determined that biofilms formed in more concentrated mucus were more robust and less susceptible to mechanical and chemical challenges compared to biofilms grown in lower concentrated mucus. Neither DNA degradation nor disulfide bond reduction was sufficient to fully degrade biofilms. Mucus rehydration should remain a priority for treating CF pulmonary disease with concomitant multimechanistic biofilm degradation agents and antibiotics to clear chronic infection.

Effects of continuous and discrete boundary conditions on the movement of upper-convected maxwell and Newtonian mucus layers in coughing and sneezing.

Mucociliary clearance is an important phenomenon inside the respiratory system as a first defensive mechanism against pathogens. Therefore, any assumption considered for the mucociliary clearance and affects its functionality must be validated. The present research deals with the effects of boundary conditions on the movement of upper-convected Maxwell and high viscosity Newtonian mucus layers, numerically. Furthermore, the validity of replacing the viscoelastic mucus layer with a high viscosity Newtonian layer is evaluated. The airway surface liquid layer is considered a two-layer model including non-Newtonian mucus and Newtonian periciliary layers. Four cyclic boundary conditions are imposed at the mucus-periciliary interface as the cilia movement to obtain variations of mucociliary clearance. The upper boundary of the mucus layer is also exposed to different shear stress levels including free slip, cough, and sneeze conditions. By investigation of velocity variations inside mucus and periciliary layers, it is concluded the differences between viscoelastic and Newtonian mucus are not negligible. The maximum velocity differences between the two fluids are more than 52% and 215% during cough and sneeze, respectively. The results show there is a high order of dependency between the relaxation time and the imposed boundary conditions at the mucus-periciliary interface that leads to the invalidation of replacing two fluids with each other. Moreover, the results show substituting the viscoelastic mucus with a high viscosity Newtonian one depends on the mucus-periciliary interface boundary condition. If an independent time-varying boundary condition is used, the substitution leads to an error less than 7% under different shear stress levels. However, time-varying boundary condition shows 38% and 88% differences between high viscosity Newtonian and viscoelastic mucus layers. Furthermore, neglecting the recovery stroke leads to a velocity underestimation up to 50% by substituting viscoelastic mucus with a high viscosity Newtonian one. Therefore, replacing the viscoelastic mucus with a high viscosity Newtonian one is not acceptable for numerical simulations.

Mucus-penetrating nanoparticles based on chitosan grafted with various non-ionic polymers: Synthesis, structural characterisation and diffusion studies

Transmucosal administration offers numerous advantages for drug delivery as it usually helps to avoid first pass metabolism, provides rapid onset of action, and is a non-invasive route. Mucosal surfaces are covered by a viscoelastic mucus gel layer which acts as a protective barrier preventing the entrance of harmful substances into the human tissues. This function of mucus also inhibits the diffusion of drugs and nano-formulations and can result in a significant reduction of their efficacy. The design of mucus-penetrating nanoparticles can overcome the barrier function of mucus which may lead to better therapeutic outcomes. In this study, chitosan was chemically modified by grafting short chains of poly(ethylene glycol), poly(2-hydroxyethyl acrylate), poly(2-ethyl-2-oxazoline), or poly(N-vinyl pyrrolidone) and the resulting chitosan derivatives were used to prepare nanoparticles using an ionic gelation method with sodium tripolyphosphate. These nanoparticles were characterised using dynamic light scattering, transmission electron microscopy, small-angle neutron scattering and nanoparticle tracking analysis. Small-angle neutron scattering data revealed the presence of a large amount of water inside these nanoparticles and lack of a heterogeneous internal structure. The nanogel model with low crosslinking density is suggested as the most feasible model to describe the structure of these nanoparticles. The studies of the behaviour of these nanoparticles in bovine submaxillary mucin solutions and their penetration into sheep nasal mucosa indicated greater diffusivity of modified chitosan nanoparticles compared to unmodified chitosan nanoparticles with the best results achieved for the chitosan grafted with poly(N-vinyl pyrrolidone).

Rapid Viscoelastic Characterization of Airway Mucus Using a Benchtop Rheometer.

In muco-obstructive lung diseases (e.g., asthma, chronic obstructive pulmonary disease, cystic fibrosis) and other respiratory conditions (e.g., viral/bacterial infections), mucus biophysical properties are altered by goblet cell hypersecretion, airway dehydration, oxidative stress, and the presence of extracellular DNA. Previous studies showed that sputum viscoelasticity correlated with pulmonary function and that treatments affecting sputum rheology (e.g., mucolytics) can result in remarkable clinical benefits. In general, rheological measurements of non-Newtonian fluids employ elaborate, time-consuming approaches (e.g., parallel/cone-plate rheometers and/or microbead particle tracking) that require extensive training to perform the assay and interpret the data. This study tested the reliability, reproducibility, and sensitivity of Rheomuco, a user-friendly benchtop device that is designed to perform rapid measurements using dynamic oscillation with a shear-strain sweep to provide linear viscoelastic moduli (G', G", G*, and tan δ) and gel point characteristics (γcand σc) for clinical samples within 5 min. Device performance was validated using different concentrations of a mucus simulant, 8 MDa polyethylene oxide (PEO), and against traditional bulk rheology measurements. A clinical isolate harvested from an intubated patient with status asthmaticus (SA) was then assessed in triplicate measurements and the coefficient of variation between measurements is <10%. Ex vivo use of a potent mucus reducing agent, TCEP, on SA mucus resulted in a five-fold decrease in elastic modulus and a change toward a more "liquid-like" behavior overall (e.g., higher tan δ). Together, these results demonstrate that the tested benchtop rheometer can make reliable measures of mucus viscoelasticity in clinical and research settings. In summary, the described protocol could be used to explore the effects of mucoactive drugs (e.g., rhDNase, N-acetyl cysteine) onsite to adapt treatment on a case-by-case basis, or in preclinical studies of novel compounds.

Regional Differences in Mucociliary Clearance in the Upper and Lower Airways.

As the nasal cavity is the portal of entry for inspired air in mammals, this region is exposed to the highest concentration of inhaled particulate matter and pathogens, which must be removed to keep the lower airways sterile. Thus, one might expect vigorous removal of these substances via mucociliary clearance (MCC) in this region. We have investigated the rate of MCC in the murine nasal cavity compared to the more distal airways (trachea). The rate of MCC in the nasal cavity (posterior nasopharynx, PNP) was ∼3–4× greater than on the tracheal wall. This appeared to be due to a more abundant population of ciliated cells in the nasal cavity (∼80%) compared to the more sparsely ciliated trachea (∼40%). Interestingly, the tracheal ventral wall exhibited a significantly lower rate of MCC than the tracheal posterior membrane. The trachealis muscle underlying the ciliated epithelium on the posterior membrane appeared to control the surface architecture and likely in part the rate of MCC in this tracheal region. In one of our mouse models (Bpifb1 KO) exhibiting a 3-fold increase in MUC5B protein in lavage fluid, MCC particle transport on the tracheal walls was severely compromised, yet normal MCC occurred on the tracheal posterior membrane. While a blanket of mucus covered the surface of both the PNP and trachea, this mucus appeared to be transported as a blanket by MCC only in the PNP. In contrast, particles appeared to be transported as discrete patches or streams of mucus in the trachea. In addition, particle transport in the PNP was fairly linear, in contrast transport of particles in the trachea often followed a more non-linear route. The thick, viscoelastic mucus blanket that covered the PNP, which exhibited ∼10-fold greater mass of mucus than did the blanket covering the surface of the trachea, could be transported over large areas completely devoid of cells (made by a breach in the epithelial layer). In contrast, particles could not be transported over even a small epithelial breach in the trachea. The thick mucus blanket in the PNP likely aids in particle transport over the non-ciliated olfactory cells in the nasal cavity and likely contributes to humidification and more efficient particle trapping in this upper airway region.

Propagation and rupture of elastoviscoplastic liquid plugs in airway reopening model

The propagation and rupture of mucus plugs in human lungs is investigated experimentally by injecting synthetic mucus in a pre-wetted capillary tube. The rheology of our test liquid is thoroughly characterized, and four samples of synthetic mucus are considered in order to reproduce elastoviscoplastic regimes of physiological interest for airway reopening. Our experiments demonstrate the significant impact of the viscoplasticity and viscoelasticity of mucus. In support to our experiments, we propose a one-dimensional reduced-order model that takes into account capillarity, and elastoviscoplasticity. Our model manages to capture the cross-section averaged dynamics of the liquid plug and is used to elucidate and interpret the experimental evidence. Relying on it, we show that the liquid film thickening due to non-Newtonian effects favors plug rupture, whereas the increase of the effective viscosity due to higher yield stresses hinders plug rupture. As a result of such two effects, increasing the polymeric concentration in the mucus phase leads to a net increase of the rupture time and traveling length. Hence, non-Newtonian effects hinder airway reopening.

Nonlinear simulation of mucociliary clearance: A three- dimensional study

In this study three-dimensional (3D) numerical simulation of mucociliary clearance from the lung has been studied. The major thrust of this investigation is 3D simulation of mucociliary clearance accounting for non-linear viscoelastic characteristics of the mucus layer which is one of the most complex fluids in our body. Using a numerical code, three-dimensional unsteady flow computations have been carried out to study ciliary motion in a two-layer fluid model of the (bronchial) airway surface liquid (ASL) consisting of a Newtonian lower periciliary layer (PCL) and a nonlinear viscoelastic upper mucus layer. The projection finite difference method is used to solve the governing and constitutive equations on a staggered Eulerian grid. The immersed boundary method (IBM) is also employed to study the effect of cilia propulsive force on the fluid flow. The 5-mode nonlinear Giesekus model has been used as the constitutive equation of mucus which is characterized by nonlinear (non-Newtonian viscosity) properties. Numerical results have been devoted to study the effect of various parameters such as cilia beat frequency, cilia length as well as PCL and mucus depth on mucociliary clearance. The present 3D model shows very good agreement with previous experimental studies, while ca. 2.5-fold larger clearance rates were found for 2D models. 3D results show that cilia beating frequency and cilia length are the most critical factors affecting mucociliary clearance, while PCL depth and mucus depth have little and intermediate effect on mucus flow and hence clearance rate respectively.

On Harvesting and Handling of Porcine Jejunal Mucus: A Few Tricks of the Trade

As a heterogeneous hydrogel, mucus has evolved into a formidable physiological barrier protecting the human body from external pathogens and toxic molecules. With mucin as its primary solid component, the viscoelasticity of mucus remains dynamic and dependent upon a plethora of factors, including pathological state, food intake, and infection. Current nanomedicine research strives toward developing nanoformulations that can permeate through the mucus barrier and release the encapsulated cargo of drug molecules at the vicinity of epithelial lining or be directly absorbed into the bloodstream. However, it is difficult to mimic mucus in vitro while the ex vivo models remain inadequate or incompatible with many established microscopic platforms. The UCD School of Veterinary Medicine has a rich legacy of working with porcine gut mucus as an experimental model, while some interesting and innovative ideas were developed by researchers here to address these challenges. This article presents a snapshot of those ideas and life hacks that the author wishes to share with the nanomedicine research community.

The Biological Synthesis and the Function of Mucin 2 in Pseudomyxoma Peritonei.

Excessive mucus secretion is the most prominent feature of pseudomyxoma peritonei (PMP), which often leads to significant increase in abdominal circumference, intractable abdominal pain, progressive intestinal obstruction, abdominal organ adhesions, and cachexia. Excessive mucus secretion is also the main cause of death. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is the recommended treatment for PMP. However, recurrence is frequently observed even after CRS and HIPEC, presenting similar clinical manifestations. Mucin 2 (MUC2) is the main type of mucin in PMP and plays a key role in the progressive sclerosis of mucus. To comprehensively demonstrate the biosynthetic process and molecular features of MUC2 and to provide new directions for the development of PMP mucolytic strategies, this review systematically summarizes the molecular biology of MUC2, including MUC2 gene structure, transcription, translation, post-translational modification, tertiary structure, and factors regulating mucus viscoelasticity. The results show that MUC2 is a highly glycosylated protein, with glycan accounts for 80% to 90% of the dry weight. The assembly pattern of MUC2 is highly complicated, presenting a bead-like filament. Salt concentration, pH, mucin concentration and trefoil factor family may contribute to the increase in mucus viscoelasticity and sclerosis, which could be used to develop drugs to soften or even dissolve mucus in the future.

Drag Reduction Characteristics of Bionic Mucous Membrane Acting on the Turbulent Boundary Layer

The mucous membrane on the fish surface has excellent drag reduction performance. The mucous membrane can be regarded as the viscoelastic fluid, and a bionic friction drag reduction model is proposed with the consideration of a Carreau viscoelastic model-based mucus secretion process. Then, the drag reduction effect of the mucous membrane on the classical wall turbulence boundary layer is investigated by large-eddy simulations. Results show that the bionic mucous membrane is conducive to reducing the turbulence, and can achieve a drag reduction rate of about 14%. This study provides a hydrodynamics understanding of the drag reduction characteristics of the bionic mucous membrane.