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Biopolymer-based drug carriers are commonly used for the development of safe delivery systems. However, biopolymer-based systems are often highly sensitive to the acidic pH levels in the stomach and release most of their cargo before they have reached their point of destination. Such premature drug release combined with the resulting high dose requirements is not cost-efficient and comes with the risk of unwanted side effects on non-target tissues/organs. This problem can be mitigated by the mucin-based drug carriers developed here, which exhibit good stability at acidic pH levels as proven by dynamic light scattering and enzymatic degradation tests with pepsin. In addition, the mucin-based particles can deliver hydrophobic and hydrophilic drugs simultaneously, which is demonstrated both with experiments performed under in vitro sink conditions and with drug transport tests involving eukaryotic cells as targets. As photo-induced cross-links covalently stabilize those particles, they can release their payload over time in a sustained manner. The drug carrier system introduced here combines good stability with high drug encapsulation efficiency and very good biocompatibility and thus may be valuable for a broad spectrum of applications in biological settings.

Conventional bioreactors are typically developed for the production of planktonic bacteria or submerged biofilms. In contrast, reactors for the continuous production of biofilms at the solid-air interface are scarce, and they require specific conditions since the bacteria need to attach firmly to the surface and require a permanent supply of moisture and nutrients from below. Recently, research from the field of civil engineering has pinpointed an increased need for the production of terrestrial biofilms: several variants of Bacillus subtilis biofilms have been shown to be useful additives to mortar that increase the water repellency, and, thus, the lifetime of the cementitious material. The bioreactor introduced here allows for the continuous production of such bacterial biofilms at the solid-air interface, and they have virtually identical properties as biofilms cultivated via classical microbiological techniques. This is made possible by equipping a rotating cylinder with a porous membrane that acts as a solid growth substrate the bacterial biomass can form on. In this configuration, nutrient supply is enabled via diffusive transport of a suitable growth medium from the core volume of the cylindrical reactor to the membrane surface. In addition to cultivating bacterial biofilms, the versatile and adaptable set up introduced here also enables the growth of other microbial organisms including the yeast Saccharomyces cerevisiae and the fungus Penicillium chrysogenum.

Owing to the unhealthy lifestyle and genetic susceptibility of today's population, atherosclerosis is one of the global leading causes of life-threatening cardiovascular diseases. Although a rapid intervention is required for severe blood vessel constrictions, a systemic administration of anticoagulant drugs is not the preferred method of choice as the associated risk of bleeding complications is high. In this study, we present mechanosensitive nanogels that exhibit tunable degrees of disintegration upon exposure to different levels of stenosis. Those nanogels can be further functionalized to encapsulate charged drug molecules such as heparin, and they efficiently release their cargo when passing stenotic constrictions; however, passive drug leakage in the absence of mechanical shear stress is very low. Furthermore, heparin molecules liberated from those mechanosensitive nanogels show a similar blood clot lysis efficiency as the free drug molecules, which demonstrates that drug encapsulation into those nanogels does not interfere with the functionality of the cargo. Thus, the hemocompatible and mechanoresponsive nanogels developed here represent a smart and efficient drug delivery platform that can offer safer solutions for vascular therapy.

The viscosities of poly(3-hydroxybutyrate) (PHB) with mixed tacticities were determined as functions of temperature and shearing rate via plate–plate viscosimetry, and fitted by a combined Herschel–Bulkley–Cross–Doolittle model while applying Carvalho et al.’s single-point correction. They were compared to values of slit viscosimetry, obtained during processing at a temperature of 428 K. In both cases, measured values and fitted model parameters as a function of tacticity exhibited a discontinuous behaviour at a fraction of meso diads of 0.7. To further investigate, we calculated values of vibrational and excess free volume. We found that these correlate with structural and external properties, some of which were reported in earlier works, namely the paracrystalline contents and specific volumes of the materials at room temperature, as well as their energies of fracture during tensile testing. These, in turn, correlate with the statistical averages of relative lengths of chain segments of similar a- or iso-tacticity. Hence, we found that expressing changing tacticities simply by a continuous progression of the fraction of meso diads is insufficient to trace associated discontinuities of the flow behaviour in mixed-tacticity PHB. We conclude that free volume is generated by polymer chain conformational disorder, which should be treated on the oligomeric chain segment level.

Several challenges need to be overcome when applying nucleic acids as therapeutic agents. We developed a new way to control the onset of the release of cholesterol-conjugated oligonucleotides. Moreover, we...

Drug delivery systems that release hydrophobic drugs with zero-order kinetics remain rare and are often complicated and hard to use. In this work, we present a gellified emulsion (emulgel) that comprises oil droplets of a hydrolyzable oil entrapped in a hydrogel. In the oil, we incorporate various hydrophobic drugs and, because the oil hydrolyzes with zero-order kinetics, the release of the drugs is also linear. We tune the release period from three hours to 50 h by varying the initial oil concentration. We show that the release rate is tunable by varying the initial drug concentration. Our quantitative understanding of the system allows for predicting the drug release kinetics once the drug's partition coefficient between the oil and the aqueous phase is known. Finally, we show that our drug delivery system is fully functional after storing it at −20 °C. Cell viability studies show that the hydrolyzable oil and its hydrolysis product are non-toxic under the employed conditions. With its simplicity and versatility, our system is a promising platform for the zero-order release of the drug.

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Chemically fueled supramolecular materials offer unique properties that include spatial and temporal control and even the ability to self-heal. Indeed, a few studies have demonstrated the ability to self-heal, however, the underlying mechanisms remain unclear. Here, we designed a peptide that forms a fibrillar network upon chemical fueling. We were surprised that the hydrogel could self-heal despite the lack of dynamics in the fiber assembly and disassembly. We explain this behavior by a mechanism that involves the chemically fueled peptide molecules that cannot self-assemble due to the lack of nucleation sites. When the fibers are perturbed, new nucleation sites form that help the assembly resulting in the healing of the damaged network. Furthermore, we generalized the behavior for other peptides. We refer to this non-assembling, chemically-fueled peptide as a molecular glue. In future work, we aim to explore whether this self-healing mechanism applies to more complex structures, narrowing the gap between biological and synthetic self-assemblies.

To achieve and maintain good operability of medical devices while reducing putative side effects for the patient, a promising strategy is to tailor the surface properties of such devices as they critically dictate the tissue compatibility and the biofouling behavior. Indeed, those properties can be strongly improved by generating mucin coatings on such medical devices. However, using coatings on optical systems, e.g., contact lenses, comes with various challenges: here, the geometrical and optical characteristics of the lens may not be compromised by either the coating process or the coating itself. In this study, we show how mucin macromolecules can be attached onto the surfaces of rigid, gas permeable contact lenses while maintaining all critical lens parameters. We demonstrate that the generated coatings improve the surface wettability (contact angles are reduced from 105° to 40° and liquid film break-up times are increased from1 s to 31 s) and prevent tribological damage to corneal tissue. Additionally, such coatings are highly transparent (transmission values above 98 % compared to an uncoated sample are reached) and efficiently reduce lipid deposition to the lens surface by 90 % but fully maintain the geometrical and mechanical properties of the lenses. Thus, such mucin coatings could also be highly beneficial for other optical systems that are used in direct contact with tissues or body fluids.

The respiratory tract surface is protected from inhaled pathogens by a secreted layer of mucus rich in mucin glycoproteins. Abnormal mucus accumulation is a cardinal feature of chronic respiratory diseases but the relationship between mucus and pathogens during exacerbations is poorly understood. We identified elevations in airway MUC5AC and MUC5B concentrations during spontaneous and experimentally-induced chronic obstructive pulmonary disease (COPD) exacerbations. MUC5AC was more sensitive to changes in expression during exacerbation and was therefore more predictably associated with virus load, inflammation, symptom severity, decrements in lung function, and secondary bacterial infections. MUC5AC was functionally related to inflammation as Muc5ac-deficient (Muc5ac-/-) mice had attenuated rhinovirus (RV)-induced airway inflammation and exogenous MUC5AC glycoprotein administration augmented inflammatory responses and increased release of extracellular adenosine triphosphate (ATP) in mice and human airway epithelial cell cultures. Hydrolysis of ATP suppressed MUC5AC augmentation of rhinovirus-induced inflammation in mice. Therapeutic suppression of mucin production using an epidermal growth factor receptor (EGFR) antagonist ameliorated immunopathology in a mouse COPD exacerbation model. The coordinated virus induction of MUC5AC and MUC5B suggests that non-Th2 mechanisms trigger mucin hypersecretion during exacerbations. Our data identifies a pro-inflammatory role for MUC5AC during viral infection and suggest that MUC5AC inhibition may ameliorate COPD exacerbations.

Gaining control over the delivery of therapeutics to a specific disease site is still very challenging. However, especially when cytotoxic drugs such as chemotherapeutics are used, the importance of a control mechanism that can differentiate "sick" target cells from the surrounding healthy tissue is pivotal. Here, we designed a nanoparticle-based drug delivery process, which releases an active agent only in the presence of a specific trigger DNA sequence. With this strategy, we are able to initiate the release of therapeutics into the cytosol with high efficiency. Furthermore, we demonstrate how an endogenous marker (e.g., a specific miRNA sequence) that is overexpressed in the initial phases of certain cancer types can be used as a stimulus to autonomously initiate intracellular drug release-and only in cells where this pathophysiological marker is present. We expect that this precisely controlled delivery mechanism can facilitate the design of site-specific treatments for such diseases, where an overexpression of signature oligonucleotide sequences has been identified.

In living systems, fuel-driven assembly is ubiquitous, and examples include the formation of microtubules or actin bundles. These structures have inspired researchers to develop synthetic counterparts, leading to exciting new behaviors in man-made structures. However, most of these examples are serendipitous discoveries because clear design rules do not yet exist. In this work, we show design rules to drive peptide self-assembly regulated by a fuel-driven reaction cycle. We demonstrate that, by altering the ratio of attractive to repulsive interactions between peptides, the behavior can be toggled between no assembly, fuel-driven dissipative self-assembly, and a state in which the system is permanently assembled. These rules can be generalized for other peptide sequences. In addition, our finding is explained in the context of the energy landscapes of self-assembly. We anticipate that our design rules can further aid the field and help the development of autonomous materials with life-like properties.

A stable, good coverage of the corneal tissue by the tear film is essential for protecting the eye. Contact lenses, however, constitute a foreign body that separates the tear film into two thinner layers, which are then more vulnerable toward disruption. This effect is even more pronounced if the contact lenses possess an insufficient surface wettability, which, in addition to friction, is suggested to be linked to discomfort and damage to the ocular surface. In this study, we establish covalent surface coatings with mucin macromolecules to overcome this issue for pure silicone contact lenses. This material class, which outperforms state-of-the-art silicone hydrogels in terms of oxygen permeability, is not yet used for commercial contact lens applications, which is due to its strongly hydrophobic surface characteristics. The applied process stably attaches a transparent mucin layer onto the contact lenses and thereby establishes hydrophilic surfaces that not only prevent lipid adsorption but also interact very well with liquid environments. Most importantly, however, we show that those mucin coatings are indeed able to prevent wear formation on corneal tissue that is subjected to the tribological stress applied by a contact lens. Our results open up great possibilities for a variety of hydrophobic materials that are, to date, not suitable for a contact lens application. Furthermore, the ability of mucin coatings to reduce wear in a tissue/synthetic material contact might be also beneficial for other biomedical applications.

The ingress of water into mortar and concrete is an ongoing problem which can reduce the lifetime of cementitious structures. Commonly used approaches that aim at preventing water ingress mainly em...

With the “many-headed” slime mold Physarum polycelphalum having been voted the unicellular organism of the year 2021 by the German Society of Protozoology, we are reminded that a large part of nature's huge variety of life forms is easily overlooked – both by the general public and researchers alike. Indeed, whereas several animals such as mussels or spiders have already inspired many scientists to create novel materials with glue-like properties, there is much more to discover in the flora and fauna. Here, we provide an overview of naturally occurring slimy substances with adhesive properties and categorize them in terms of the main chemical motifs that convey their stickiness, i.e., carbohydrate-, protein-, and glycoprotein-based biological glues. Furthermore, we highlight selected recent developments in the area of material design and functionalization that aim at making use of such biological compounds for novel applications in medicine – either by conjugating adhesive motifs found in nature to biological or synthetic macromolecules or by synthetically creating (multi-)functional materials, which combine adhesive properties with additional, problem-specific (and sometimes tunable) features., Graphical abstract Image 1

With big datasets and highly efficient algorithms becoming increasingly available for many problem sets, rapid advancements and recent breakthroughs achieved in the field of machine learning encourage more and more scientific fields to make use of such a computational data analysis. Still, for many research problems, the amount of data available for training a machine learning (ML) model is very limited. An important strategy to combat the problems arising from data sparsity is feature elimination—a method that aims at reducing the dimensionality of an input feature space. Most such strategies exclusively focus on analyzing pairwise correlations, or they eliminate features based on their relation to a selected output label or by optimizing performance measures of a certain ML model. However, those strategies do not necessarily remove redundant information from datasets and cannot be applied to certain situations, e.g., to unsupervised learning models. Neither of these limitations applies to the network-based, correlation-driven redundancy elimination (NETCORE) algorithm introduced here, where the size of a feature vector is reduced by considering both redundancy and elimination efficiency. The NETCORE algorithm is model-independent, does not require an output label, and is applicable to all kinds of correlation topographies within a dataset. Thus, this algorithm has the potential to be a highly beneficial preprocessing tool for various machine learning pipelines.

Thin materials made from elastomeric polymers such as polydimethylsiloxane (PDMS) and polyurethane (PU) can be both, compliant and resilient. Their mechanical robustness and flexibility will make them great candidates for applications in the human body where space is limited and repeated deformations occur. Nonetheless, current medical applications of elastomeric foil-like products are mainly restricted to inflatable balloon parts of stents or intubation tubes. Here, a key limiting factor is the autohesive behavior of those foils, that is, their propensity to stick to themselves. This property impedes handling and processing and can also interfere with the designated tasks of such foils. To mitigate this undesired behavior, different bio-macromolecular coatings are applied here and assess their influence on the autohesive behavior, flexibility, and transparency of the materials. A non-covalent, dopamine-assisted coating approach is compared to a covalent coating strategy employing carbodiimide chemistry and investigated both, anionic and cationic macromolecules as top layers. The results show that especially the carbodiimide-mediated mucin coating can efficiently suppress the autohesive behavior of the foils while maintaining the flexibility and transparency of the material. Thus, such coatings can not only broaden the medical application range of foil-based elastomeric devices but may also prove beneficial for applications in soft robotics.

Similar to how CRISPR has revolutionized the field of molecular biology, machine learning may drastically boost research in the area of materials science. Machine learning is a fast-evolving method that allows for analyzing big data and unveiling correlations that otherwise would remain undiscovered. It may hold invaluable potential to engineer novel functional materials with desired properties, a field, which is currently limited by time-consuming trial and error approaches and our limited understanding of how different material properties depend on each other. Here, we apply machine learning algorithms to classify complex biological materials based on their microtopography. With this approach, the surfaces of different variants of biofilms and plant leaves can not only be distinguished but also correctly classified according to their wettability. Furthermore, an importance ranking provided by one of the algorithms allows us to identify those surface features that are critical for a successful sample classification. Our study exemplifies how machine learning can contribute to the analysis and categorization of complex surfaces, a tool, which can be highly useful for other areas of materials science, such as damage assessment as well as adhesion or friction studies.

A new family of sustainable tackifying agents with adjustable glass transition temperatures was prepared via torrefaction of outer birch bark waste. The application of the obtained betulin esters a...

Most medical therapies require repeated, sequential administration of therapeutic agents in well-defined intervals and over extended time windows. Typically, the patient is in charge of applying the individual drug doses, and insufficient patient compliance reduces the efficiency of the treatment. Therefore, the development of a smart delivery mechanism releasing therapeutic agents in a pre-defined, time-controlled fashion would be beneficial for many medical treatments. Here, we present a DNA-mediated release cascade which allows for precisely controlling the sequential delivery of several different nanoparticles. By using complementary DNA sequences, nanoparticle aggregates are created, embedded into distinct layers of a hydrogel and released by triggering aggregate dispersal. This mechanism is compatible with physiological conditions as the release cascade is initiated by exposing the nanoparticle-loaded gel to physiological salt concentrations. Moreover, we show that the reservoir hydrogel can be enriched with biopolymers to receive charge-selective release properties towards small molecules - without interfering with the DNA-based release cascade. Owing to the excellent reproducibility, precision and effectiveness of the presented mechanism, a similar DNA-mediated release avalanche may lead to the development of autonomous and robust delivery systems, which minimize the possibility of pharmaceutical therapy failure due to patient non-compliance.

Production and secretion of biomolecules can provide new emergent functionalities to the synthesizing organism. In particular, the secretion of extracellular polymeric substances (EPS) by biofilm forming bacteria creates a biofilm matrix that protects the individual bacteria within the biofilm from external stressors such as antibiotics, chemicals and shear flow. Although the main matrix components of biofilms formed by Bacillus subtilis are known, it remains unclear how these matrix components contribute to the erosion stability of B. subtilis biofilms. Here, we combine different biophysical techniques to assess this relation. In particular, we quantify the importance of specific biofilm matrix components on the erosion behavior of biofilms formed by the well-studied Bacillus subtilis NCIB 3610. We find that the absence of biofilm matrix components decreases the erosion stability of NCIB 3610 biofilms in water, largely by abolishing the hydrophobic surface properties of the biofilm and by reducing the biofilm stiffness. However, the erosion resistance of NCIB 3610 biofilms is strongly increased in the presence of metal ions or the antibiotic ciprofloxacin. In the first case, unspecific ionic cross-linking of biofilm components or individual bacteria seems to be responsible for the observed effect, and in the second case there seems to be an unspecific interaction between the antibiotic and the biofilm matrix. Taken together, our results emphasize the importance of the biofilm matrix to reduce biofilm erosion and give insights into how the specific biomolecules interact with certain chemicals to fulfill this task.

Commercial mucin glycoproteins are routinely used as a model to investigate the broad range of important functions mucins fulfill in our bodies, including lubrication, protection against hostile germs, and the accommodation of a healthy microbiome. Moreover, purified mucins are increasingly selected as building blocks for multifunctional materials, i.e., as components of hydrogels or coatings. By performing a detailed side-by-side comparison of commercially available and lab-purified variants of porcine gastric mucins, we decipher key molecular motifs that are crucial for mucin functionality. As two main structural features, we identify the hydrophobic termini and the hydrophilic glycosylation pattern of the mucin glycoprotein; moreover, we describe how alterations in those structural motifs affect the different properties of mucins-on both microscopic and macroscopic levels. This study provides a detailed understanding of how distinct functionalities of gastric mucins are established, and it highlights the need for high-quality mucins-for both basic research and the development of mucin-based medical products.

Even though medical devices have improved a lot over the past decades, there are still issues regarding their anti-biofouling properties and tribological performance, and both aspects contribute to the short- and long-term failure of these devices. Coating these devices with a biocompatible layer that reduces friction, wear, and biofouling at the same time would be a promising strategy to address these issues. Inspired by the adhesion mechanism employed by mussels, here, dopamine is made use of to immobilize lubricious mucin macromolecules onto both manufactured commercial materials and real medical devices. It is shown that purified mucins successfully adsorb onto a dopamine pre-coated substrate, and that this double-layer is stable toward mechanical challenges and storage in aqueous solutions. Moreover, the results indicate that the dopamine/mucin double-layer decreases friction (especially in the boundary lubrication regime), reduces wear damage, and provides anti-biofouling properties. The results obtained in this study show that such dopamine/mucin double-layer coatings can be powerful candidates for improving the surface properties of medical devices such as catheters, stents, and blood vessel substitutes.

The aim of the present work was to evaluate the changes in instrumental measurements and dynamic sensory properties of chocolate as affected by the partial and total substitution of sucrose by dodecenyl-succinylated inulin upon storage. The results of textural, surface topology, and tribological properties of non-stored chocolates were found to be a function of modified inulin replacement, where an increase in modified inulin ratio allowed an increase in hardness, roughness, and friction coefficient. Compared to non-stored samples, the deterioration of textural properties after storage was inhibited in chocolate containing higher levels of modified inulin. Higher modified inulin ratios did not also induce an important change in NMR proton mobility, roughness, and friction coefficient upon storage. Confocal Raman microscopy revealed modified inulin located around sucrose and cocoa particles dispersed in fat phase, especially at the higher ratios. Temporal Dominance of Sensations (TDS) curves of non-stored samples elucidated that firmness was a dominant perception at the beginning of mastication, followed by melting rate, while cocoa flavor was experienced at the end of evaluation. However, these attributes were not perceived in stored chocolate with the lowest modified inulin. A PCA was performed to compare TDS scores and instrumental readings, showing a high correlation between instrumental measurement of hardness, friction coefficient, and NMR relaxation times and TDS score of firmness, bitterness, astringency, and melting rate. This work shows a new perspective to use biopolymeric surfactant for producing low-calorie chocolate, considering that hydrophobically modified inulin can diminish production costs and facilitate low-calorie product development.

Hydrogels made of crosslinked macromolecules used in regenerative medi-cine technologies can be designed to affect the fate of surrounding cells and tissues in defined ways. Their function typically depends on the type and number of bioactive moieties such as receptor ligands present in the hydrogel. However, the detail in how such moieties are presented to cells can also be instrumental. In this work, how the crosslinking architecture of a hydrogel can affect its bioactivity is explored. It is shown that bovine submaxillary mucins, a highly glycosylated and immune-modulating protein, exhibit strikingly different bioactivities whether they are crosslinked through their glycans or their protein domains. Both the susceptibility to enzymatic degradation and macrophage response are affected, while rheological proper-ties and barrier to diffusion are mostly unaffected. The results suggest that crosslinking architecture affects the accessibility of the substrate to pro-teases and the pattern of sialic acid residues exposed to the macrophages. Thus, modulating the accessibility of binding sites through the choice of the crosslinking strategy appears as a useful parameter to tune the bioactivity of hydrogel-based systems

Over millennia, bacteria have developed clever strategies to build biopolymer-based communities in which they can survive even extremely challenging conditions. Such bacterial biofilms come with a broad range of fascinating material properties that-in settings such as medicine, food production, or other areas of industry-make it difficult to remove or inactivate them: they can stick to many surfaces, repel water and oils, and can even transport electrons. Inspired by the outstanding versatility and sturdiness of such bacterial biofilms, material scientists have set out to harness those properties and to create bacterial materials for different applications. However, as the range of technological applications employing biofilms keeps expanding, improved material properties or broader functionalities are desired. Here, such attempts where materials with improved properties were created by making use of either natural or modified bacterial biofilms are reviewed. The areas in which those bacterial materials may be used range from agriculture and (environmental) biotechnology over biomedical and electrical engineering to construction engineering.

Many supramolecular materials in biological systems are driven to a nonequilibrium state by the irreversible consumption of high-energy molecules such as ATP or GTP. As a result, they exhibit unique dynamic properties such as a tunable lifetime, adaptivity or the ability to self-heal. In contrast, synthetic counterparts that exist in or close to equilibrium are controlled by thermodynamic parameters and therefore lack these dynamic properties. To mimic biological materials more closely, synthetic self-assembling systems have been developed that are driven out of equilibrium by chemical reactions. This protocol describes the synthesis and characterization of such an assembly, which is driven by carbodiimide fuels. Depending on the amount of chemical fuel added to the material, its lifetime can be tuned. In the first step, the protocol details the synthesis and purification of the peptide-based precursors for the fuel-driven assemblies by solid-phase peptide synthesis. Then, we explain how to analyze the kinetic response of the precursors to a carbodiimide-based chemical fuel by HPLC and kinetic models. Finally, we detail how to study the emerging assembly’s macro- and microscopic properties by time-lapse photography, UV-visible spectroscopy, shear rheology, confocal laser scanning microscopy and electron microscopy. The procedure is described using the example of a colloid-forming precursor Fmoc-E-OH and a fiber-forming precursor Fmoc-AAD-OH to emphasize the differences in characterization depending on the type of assembly. The characterization of a precursor’s transient assembly can be done within 5 d. The synthesis and purification of a peptide precursor requires 2 d of work. This protocol describes the setup and characterization of a supramolecular assembly of small precursors into colloids or fibers driven by carbodiimide fuels. When the fuel is spent, the reaction reverses to form the initial peptides or amino acids.

Mucin glycoproteins are the matrix-forming key components of mucus, the innate protective barrier protecting us from pathogenic attack. However, this barrier is constantly challenged by mucin-degrading enzymes, which tend to target anionic glycan chains such as sulfate groups and sialic acid residues. Here, we demonstrate that the efficiency of both unspecific and specific binding of small molecules to mucins is reduced when sulfate groups are enzymatically removed from mucins; this is unexpected because neither of the specific mucin-binding partners tested here targets these sulfate motifs on the mucin glycoprotein. Based on simulation results obtained from a numerical model of the mucin macromolecule, we propose that anionic motifs along the mucin chain establish intramolecular repulsion forces which maintain an elongated mucin conformation. In the absence of these repulsive forces, the mucin seems to adopt a more compacted structure, in which the accessibility of several binding sites is restricted. Our results contribute to a better understanding on how different glycans contribute to the broad spectrum of functions mucin glycoproteins have. © 2020 American Chemical Society.

Most biofilm research has so far focused on investigating biofilms generated by single bacterial strains. However, such single-species biofilms are rare in nature where bacteria typically coexist with other microorganisms. Although, from a biological view, the possible interactions occurring between different bacteria are well studied, little is known about what determines the material properties of a multi-species biofilm. Here, we ask how the co-cultivation of two B. subtilis strains affects certain important biofilm properties such as surface topography and wetting behavior. We find that, even though each daughter colony typically resembles one of the parent colonies in terms of morphology and wetting, it nevertheless exhibits a significantly different surface topography. Yet, this difference is only detectable via a quantitative metrological analysis of the biofilm surface. Furthermore, we show that this difference is due to the presence of bacteria belonging to the ‘other’ parent strain, which does not dominate the biofilm features. The findings presented here may pinpoint new strategies for how biofilms with hybrid properties could be generated from two different bacterial strains. In such engineered biofilms, it might be possible to combine desired properties from two strains by co-cultivation.

Erosion resistance is one of the advantages bacteria gain by producing biofilms. While it is undesirable for us humans when biofilms grow on medical devices or industrial pipelines, biofilms with a high erosion resistance can be advantageous for biotechnological applications. Here, we demonstrate how the erosion resistance of B. subtilis NCIB 3610 biofilms can be enhanced by integrating foreign (bio)polymers such as γ-polyglutamate (PGA), alginate and polyethylene glycol (PEG) into the matrix during biofilm growth.Artificial enrichment of the NCIB 3610 biofilms with these biopolymers causes a significant increase in the erosion resistance by slightly changing the surface topography: A decreased cavity depth on the surface results in an alteration in the mode of surface superhydrophobicity, and we obtain a state that is located somewhere between rose-petal like and lotus-like wetting resistance. Surprisingly, the viscoelastic and microscopic penetration properties of the biofilms are not affected by the artificial incorporation of (bio)polymers. As we obtained similar results with all the biopolymers tested (which differ in terms of charge and molecular weight), this indicates that a variety of different (bio)polymers can be employed for a similar purpose.The method introduced here may present a promising strategy for engineering beneficial biofilms such, that they become more stable towards shear forces caused by flowing water but, at the same time, remain permeable to nutrients or other molecules.

Mucin glycoproteins, the macromolecular components of mucus, combine a broad range of biomedically important properties. Among those is the ability of mucin solutions to act as excellent lubricants. However, to be able to use purified, endogenous mucin glycoproteins as components of a biomedical product, the mucins need to be sterile; this, in turn, makes it necessary to subject the mucins to quite harsh physical treatments, such as heat exposure, autoclaving, UV-, or γ-irradiation, which might compromise the functionality of the glycoproteins. Here, it is shown that mucins are indeed able to withstand most of those treatments without suffering significant lubrication impairment or structural degradation. Among those treatments, which left the mucins unharmed, γ-irradiation is identified to be the most powerful one in terms of inactivating microbial contaminations. The obtained results demonstrate a remarkable sturdiness of mucins, which opens up broad possibilities for them to be further processed into materials, e.g., as parts of biomedical products.

Unwanted formation of bacterial biofilms can cause problems in both the medical sector and industrial settings. However, removing them from surfaces remains an ongoing challenge since biofilm bacteria efficiently protect themselves from external influences such as mechanical shear forces by embedding themselves into a matrix of extracellular polymeric substances. Here, we discuss microscopic principles, which are responsible for alterations in the viscoelastic properties of biofilms upon contact with metal ions. We suggest that it is a combination of mainly two parameters, that decides if biofilm stiffening occurs or not: the ion size and the detailed configuration of polyanionic macromolecules from the biofilm matrix. Our results provide new insights in the molecular mechanisms that govern the mechanical properties of biofilms. Also, they indicate that hydrogels comprising purified biopolymers can serve as suitable model systems to reproduce certain aspects of biofilm mechanics – provided that the correct biopolymer is chosen.

Mucins are high molar mass glycoproteins that assume an extended conformation and can assemble into mucus hydrogels that protect our mucosal epithelium. In nature, the challenging task of generating a mucus layer, several hundreds of micrometers in thickness, from micrometer-sized cells is elegantly solved by the condensation of mucins inside vesicles and their on-demand release from the cells where they suddenly expand to form the extracellular mucus hydrogel. We aimed to recreate and control the process of compaction for mucins, the first step toward a better understanding of the process and creating biomimetic in vivo delivery strategies of macromolecules. We found that by adding glycerol to the aqueous solvent, we could induce drastic condensation of purified mucin molecules, reducing their size by an order of magnitude down to tens of nanometers in diameter. The condensation effect of glycerol was fully reversible and could be further enhanced and partially stabilized by cationic cross-linkers such as calcium and polylysine. The change of structure of mucins from extended molecules to nano-sized particles in the presence of glycerol translated into macroscopic rheological changes, as illustrated by a dampened shear-thinning effect with increasing glycerol concentration. This work provides new insight into mucin condensation, which could lead to new delivery strategies mimicking cell release of macromolecules condensed in vesicles such as mucins and heparin.

Here, we introduce a custom-made setup which allows for performing oscillatory friction measurements using a commercial shear rheometer as a technical platform. The presented measuring head can hold both artificial and biological materials as probing pins, and the sample holder is designed such that it enables measurements on a broad range of materials including technical materials such as steel and PTFE, kidney-shaped PDMS layers, and cylindrical cartilage tissue samples. Control measurements performed with an established rotational tribology setup demonstrate that the friction coefficients obtained both in the presence and absence of macromolecular lubricants agree very well with those published in the literature. Finally, we show pilot experiments in which we probe friction at the lateral interface between two different materials. For this interfacial tribology geometry, we also quantify wear generation by means of optical profilometry. © 2018 Elsevier Ltd

One of the main challenges in the field of drug delivery remains the development of strategies to efficiently transport pharmaceuticals across mucus barriers, which regulate the passage and retention of molecules and particles in all luminal spaces of the body. A thorough understanding of the molecular mechanisms, which govern such selective permeability, is key for achieving efficient translocation of drugs and drug carriers. For this purpose, model systems based on purified mucins can contribute valuable information. In this review, we summarize advances that were made in the field of drug delivery research with such mucin-based model systems: First, we give an overview of mucin purification procedures and discuss the suitability of model systems reconstituted from purified mucins to mimic native mucus. Then, we summarize techniques to study mucin binding. Finally, we highlight approaches that made use of mucins as building blocks for drug delivery platforms or employ mucins as active compounds.

A decade ago, environmental issues, such as air pollution and the contamination of the oceans with microplastic, were prominently communicated in the media. However, these days, political topics, as well as the ongoing COVID-19 pandemic, have clearly taken over. In spite of this shift in focus regarding media representation, researchers have made progress in evaluating the possible health risks associated with particulate contaminations present in water and air. In this review article, we summarize recent efforts that establish a clear link between the increasing occurrence of certain pathological conditions and the exposure of humans (or animals) to airborne or waterborne particulate matter. First, we give an overview of the physiological functions mucus has to fulfill in humans and animals, and we discuss different sources of particulate matter. We then highlight parameters that govern particle toxicity and summarize our current knowledge of how an exposure to particulate matter can be related to dysfunctions of mucosal systems. Last, we outline how biophysical tools and methods can help researchers to obtain a better understanding of how particulate matter may affect human health. As we discuss here, recent research has made it quite clear that the structure and functions of those mucosal systems are sensitive toward particulate contaminations. Yet, our mechanistic understanding of how (and which) nano- and microparticles can compromise human health via interacting with mucosal barriers is far from complete.

In the last decade, biological additives have gained increased attention as admixtures to cement based materials. One example are bacterial additives, which can improve the wetting resistance and/or the mechanical properties of cementitious materials. However, the production process of most bacterial additives investigated so far is typically time consuming and comparably expensive. Here, we investigate six different commercially available bacterial spores as an alternative bacterial additive to mortar and characterize the wetting resistance, capillary water uptake, and mechanical properties of the resulting hybrid mortar formulations. Our results imply that selected bacterial spores are indeed able to enhance the water-resistance of mortar; however, compared to other bacterial additives such as biofilm, the overall performance of the resulting hybrid material is decent but still inferior.

Quantifying surface damage on articular cartilage after exposure of the tissue to extreme or prolonged mechanical stress is not only relevant for evaluating clinically relevant alterations, e.g. when the physiological lubrication mechanisms fail, but also useful for assessing the suitability of artificial cartilage replacement materials, implants or synovia-mimetic lubricants. Here, we establish a systematic quantification method for cartilage wear formation which is based on optical profilometry – a variant of confocal microscopy. With this approach, we compare three different macromolecular lubricants, i.e. solutions containing either hyaluronic acid, lubricin or porcine gastric mucin. Depending on the counter material used for tribological testing and the macromolecule used for lubrication, we detect different types of tissue damage which we quantify with suitable topographical parameters. In our setup, mucin solutions outperform the other two lubricants: when using mucin solutions for lubrication, we do not find any signs of topographical alterations on the cartilage surface. Our results underscore the supreme protective abilities of mucin solutions - even on biological surfaces where they do not occur physiologically. © 2017 Elsevier Ltd

The production of biomolecules can provide new functionalities to the synthesizing organism. One important example is the secretion of extracellular polymeric substances (EPS) by biofilm forming bacteria. This biofilm matrix protects the individual bacteria within the biofilm from external stressors such as antibiotics, chemicals and shear flow. Previous studies have determined several main matrix components of biofilms formed by Bacillus subtilis. However, how these matrix components influence the growth behavior and final dimensions of B. subtilis biofilms has not yet been determined. Here, we combine different experimental techniques with theoretical modeling to assess this relation. In particular, we quantify the area covered by the biofilm and the biofilm height by performing time-lapse microscopy and light profilometry, respectively. We study the development of biofilms formed by two wild-type strains (B-1 and NCIB 3610) differing in their matrix composition and NCIB 3610 mutant strains lacking the ability to produce specific EPS. Based on the experimentally obtained growth dynamics, we develop a mathematical model that allows us to quantify the influence of three key biofilm matrix components on the final NCIB 3610 biofilm colony dimensions. In detail, we show that two matrix components, the exopolysaccharide produced by the epsA-O operon and the surface layer protein BslA control the area covered by the biofilm colony. The height of these mature biofilm colonies is mostly affected by BslA. Together, our results emphasize the importance of the biofilm matrix composition for biofilm growth and the final dimensions of mature B. subtilis NCIB 3610 biofilm colonies.

Recent research indicates that the progression of Parkinson's disease can start from neurons of the enteric nervous system, which are in close contact with the gastrointestinal epithelium: α-synuclein molecules can be transferred from these epithelial cells in a prion-like fashion to enteric neurons. Thin mucus layers constitute a defense line against the exposure of noninfected cells to potentially harmful α-synuclein species. We show that - despite its mucoadhesive properties - α-synuclein can translocate across mucin hydrogels, and this process is accompanied by structural rearrangements of the mucin molecules within the gel. Penetration experiments with different α-synuclein variants and synthetic peptides suggest that two binding sites on α-synuclein are required to accomplish this rearrangement of the mucin matrix. Our results support the notion that the translocation of α-synuclein across mucus barriers observed here might be a critical step in the infection of the gastrointestinal epithelium and the development of Parkinson's disease.