Biointerphases最新文献

In beam-based ionization methods, the substrate plays an important role on the desorption mechanism of molecules from surfaces. Both the specific orientation that a molecule adopts at a surface and the strength of the molecule-surface interaction can greatly influence desorption processes, which in turn will affect the ion yield and the degree of in-source fragmentation of a molecule. In the beam-based method of secondary ion mass spectrometry (SIMS), in-source fragmentation can be significant and molecule specific due to the hard ionization method of using a primary ion beam for molecule desorption. To investigate the role of the substrate on orientation and in-source fragmentation, we have used atomistic simulations-molecular dynamics in combination with density functional theory calculations-to explore the desorption of a sphingolipid (palmitoylsphingomyelin) from a model surface (gold). We then compare SIMS data from this model system to our modeling findings. Using this approach, we found that the combined adsorption and binding energy of certain bonds associated with the headgroup fragments (C₃H₈N⁺, C₅H₁₂N⁺, C₅H₁₄NO⁺, and C₅H₁₅PNO₄ ⁺) was a good predictor for fragment intensities (as indicated by relative ion yields). This is the first example where atomistic simulations have been applied in beam-based ionization of lipids, and it presents a new approach to study biointerfacial lipid ordering effects on SIMS imaging.

The mammalian organism is continuously exposed to various biological and chemical threats from its surroundings. In order to provide protection against these threats, mammals have developed a specialized defense system at the interface with their environment. This system, known as the epidermis, is mainly composed of stratified keratinocytes organized in a complex self-renewing structure providing a mechanical and chemical barrier at the skin surface. However, numerous skin-related pathologies can interfere with the proper formation and function of the epidermal barrier. The pathogenesis of these alterations is often very complex. Understanding the changes induced in epidermal tissues by these pathologies at a molecular level is key for their treatment and prevention. In this context, this work aims at developing a thorough and reproducible characterization methodology of the human epidermis by applying ToF-SIMS to the study of an in vitro epidermal model known as reconstructed human epidermis (RHE). Indeed, although the potential of ToF-SIMS for the characterization of the mammalian skin has already been demonstrated, very few studies focus their efforts on the human epidermis itself. Here, we performed static ToF-SIMS characterizations of RHE cryosections, combining both high mass and high lateral resolution acquisitions. In addition, principal components analysis was used as a multivariate analysis tool. This contributed to the decorrelation of the complex datasets obtained from these biological systems and allowed capturing of their most statistically representative spectral features. Remarkably, this tool proved to be successful in extracting meaningful biological information from the datasets by yielding principal components distinguishing the cornified layers from the metabolically active epidermal cells. Finally, on the basis of multiple ToF-SIMS acquisitions, we showed that this methodology allows for the convenient production of experimental replicates, a key feature often difficult to achieve in ex vivo approaches.

When polymer chains are grafted to solid surfaces at sufficiently high density, they form brushes that can modify the surface properties. In particular, polymer brushes are increasingly being used to reduce friction in water-lubricated systems close to the very low levels found in natural systems, such as synovial joints. New types of polymer brush are continually being developed to improve with lower friction and adhesion, as well as higher load-bearing capacities. To complement experimental studies, molecular simulations are increasingly being used to help to understand how polymer brushes reduce friction. In this paper, we review how molecular simulations of polymer brush friction have progressed from very simple coarse-grained models toward more detailed models that can capture the effects of brush topology and chemistry as well as electrostatic interactions for polyelectrolyte brushes. We pay particular attention to studies that have attempted to match experimental friction data of polymer brush bilayers to results obtained using molecular simulations. We also critically look at the remaining challenges and key limitations to overcome and propose future modifications that could potentially improve agreement with experimental studies, thus enabling molecular simulations to be used predictively to modify the brush structure for optimal friction reduction.

We present a versatile one-pot synthesis method for creating surface-anchored orthogonal gradient networks using a small bi-functional gelator, 4-azidosulfonylphenethyltrimethoxysilane (4-ASPTMS). The sulfonyl azide (SAz) group of 4-ASPTMS is UV (≤254 nm) and thermally active (≥100 °C) and, thus, enables us to vary the cross-link density in orthogonal directions by controlling the activation of SAz groups via UV and temperature means. We deposit a thin layer (∼200 nm) of a mixture comprising ∼90% precursor polymer and ∼10% 4-ASPTMS in a silicon wafer. Upon UV irradiation or annealing the layers, SAz releases nitrogen by forming singlet and triplet nitrenes that concurrently react with any C-H bond in the vicinity leading to sulfonamide cross-links. Condensation among trimethoxy groups in the bulk connects 4-ASPTMS units and completes the cross-linking. Simultaneously, 4-ASPTMS near the substrate reacts with surface-bound -OH motifs that anchor the cross-linked polymer chains to the substrate. We demonstrate the generation of orthogonal gradient network coatings exhibiting cross-link density (or stiffness) gradients in orthogonal directions using such a simple process.

Phase separation in biological membranes is crucial for proper cellular functions, such as signaling and trafficking, as it mediates the interactions of condensates on membrane-bound organelles and transmembrane transport to targeted destination compartments. The separation of a lipid bilayer into phases and the formation of lipid rafts involve the restructuring of molecular localization, their immobilization, and local accumulation. By understanding the processes underlying the formation of lipid rafts in a cellular membrane, it is possible to reconstitute this phenomenon in synthetic biomimetic membranes, such as hybrids of lipids and polymers or membranes composed solely of polymers, which offer an increased physicochemical stability and unlimited possibilities of chemical modification and functionalization. In this article, we relate the main lipid bilayer phase transition phenomenon with respect to hybrid biomimetic membranes, composed of lipids mixed with polymers, and fully synthetic membranes. Following, we review the occurrence of phase separation in biomimetic hybrid membranes based on lipids and/or direct lipid analogs, amphiphilic block copolymers. We further exemplify the phase separation and the resulting properties and applications in planar membranes, free-standing and solid-supported. We briefly list methods leading to the formation of such biomimetic membranes and reflect on their improved overall stability and influence on the separation into different phases within the membranes. Due to the importance of phase separation and compartmentalization in cellular membranes, we are convinced that this compiled overview of this phenomenon will be helpful for any researcher in the biomimicry area.

Developing molecular models to capture the complex physicochemical architecture of the bacterial cell wall and to study the interaction with antibacterial molecules is an important aspect of assessing and developing novel antimicrobial molecules. We carried out molecular dynamics simulations using an atomistic model of peptidoglycan to represent the architecture for Gram-positive S. aureus. The model is developed to capture various structural features of the Staphylococcal cell wall, such as the peptide orientation, area per disaccharide, glycan length distribution, cross-linking, and pore size. A comparison of the cell wall density and electrostatic potentials is made with a previously developed cell wall model of Gram-negative bacteria, E. coli, and properties for both single and multilayered structures of the Staphylococcal cell wall are studied. We investigated the interactions of the antimicrobial peptide melittin with peptidoglycan structures. The depth of melittin binding to peptidoglycan is more pronounced in E. coli than in S. aureus, and consequently, melittin has greater contacts with glycan units of E. coli. Contacts of melittin with the amino acids of peptidoglycan are comparable across both the strains, and the D-Ala residues, which are sites for transpeptidation, show enhanced interactions with melittin. A low energetic barrier is observed for translocation of a naturally occurring antimicrobial thymol with the four-layered peptidoglycan model. The molecular model developed for Gram-positive peptidoglycan allows us to compare and contrast the cell wall penetrating properties with Gram-negative strains and assess for the first time binding and translocation of antimicrobial molecules for Gram-positive cell walls.

Nitrile hydratase (NHase, EC 4.2.1.84) is an excellent biocatalyst that catalyzes the hydration of nitrile substances to their corresponding amides. Given its catalytic specificity and eco-friendliness, NHase has extensive applications in the chemical, pharmaceutical, and cosmetic industries. To improve the affinity between Rhodococcus erythropolis CCM2595-derived NHase (ReNHase) and adiponitrile, this study used a semirational design to improve the efficiency of ReNHase in catalyzing the generation of 5-cyanopentanamide from adiponitrile. Enzyme kinetics analysis showed that Km of the mutant ReNHase^B:G196Y was 3.265 mmol l^-1, which was lower than that of the wild-type NHase. The affinity of the mutant ReNHase^B:G196Y to adiponitrile was increased by 36.35%, and the efficiency of the mutant ReNHase^B:G196Y in catalyzing adiponitrile to 5-cyanopentamide was increased by 10.11%. The analysis of the enzyme-substrate interaction showed that the hydrogen bond length of the mutant ReNHase^B:G196Y to adiponitrile was shortened by 0.59 Å, which enhanced the interaction between the mutant and adiponitrile and, thereby, increased the substrate affinity. Similarly, the structural analysis showed that the amino acid flexibility near the mutation site of ReNHase^B:G196Y was increased, which enhanced the binding force between the enzyme and adiponitrile. Our work may provide a new theoretical basis for the modification of substrate affinity of NHase and increase the possibility of industrial applications of the enzyme.

Generally, the anchoring of inorganic nanoparticles onto the surface of fibers faces the problem of poor stability, which limits the wide application of nanoparticle functionalized fibers. Herein, nanofibers with shell-core structures were constructed by coaxial electrospinning of two polymers with different melting points (T_m). Polyglycolic acid (PGA, T_m = 225 °C) was employed as the core layer, while polycaprolactone (PCL, T_m = 60 °C) was used as the shell layer. Silver nanoparticles (AgNPs) were electrosprayed on the nanofibers and the shell layer (PCL) was heated and melted to bond the AgNPs, thus realizing a stable AgNP-composited nanofiber for the construction of antibacterial functional surface. By regulating the shell-core flow ratio and the condition for heat treatment, the appropriate thickness of the shell layer was obtained with a flow ratio of 3:1 (PCL:PGA). The optimal composite structure was constructed when the thermal bonding was taken under 80 °C for 5 min. Furthermore, it was found that the composite nanofibers prepared by thermal bonding had better hydrophilicity, mechanical property, and AgNPs bonding stability, and their antibacterial rate against Staphylococcus aureus (S. aureus) reached over 97%. Overall, a facile and universal method for the preparation of nanoparticle-anchored nanofibers was established in this study. The robust nanoparticle-composited nanofibers are promising for applications in optoelectronic devices, electrode materials, and so on.

The active ingredients of natural herbs have been extracted to act on different targets in the body to exert multiple effects. However, traditional oral administration and intravenous injection of herbal medicines are also susceptible to many side effects. Transdermal drug delivery by microneedles can overcome the shortcomings of these traditional drug delivery systems. The active ingredients of natural herbs can be delivered to the dermis or the connective tissue layer by five types of microneedles: solid, hollow, coated, dissolving, and hydrogel. Subsequently, the herbal ingredients are delivered to different target points of the body through body circulation to exert their effects. In this study, we classified the microneedles that can deliver the active ingredients of natural herbs and summarized their advantages and disadvantages as well as their preparation methods and applications, to guide the development and clinical applications of other herbal transdermal microneedles.

This study investigated CuO and ZnO nanoparticles and CuO/ZnO nanocomposites in a friendly environment with a low-cost and renewable biosynthesis method. This approach involved using Boehmeria nivea leaf extract to facilitate the growth and formation of nanocomposites with performance-enhancing phytochemicals released during the co-precipitation process. All nanoparticles/nanocomposites explored the microstructure, morphology, and point defects using FTIR, XRD, SEM, and PL characterization techniques. The synthesized CuO and ZnO nanoparticles and CuO/ZnO nanocomposites were evaluated for their antibacterial ability against both bacteria Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Combining different copper and zinc salt ratios creates different arrangements and morphologies between the CuO sheets and the spherical ZnO nanoparticles. The heterojunction of CuO/ZnO samples enhances the antibacterial effects of nanocomposites compared to pure CuO and ZnO nanoparticles. The maximum antibacterial performance was achieved at 250 ppm against E. coli and 500 ppm against S. aureus in CuO50/ZnO50 nanocomposites. This study shows that a green synthesis of CuO/ZnO nanocomposites promises great potential for environmental treatment and biochemical applications.