Biointerphases最新文献

Mechanical properties of the extracellular matrix (ECM) modulate cell-substrate interactions and influence cellular behaviors such as contractility, migration, and proliferation. Although the effects of substrate stiffness on mechanobiology have been well studied, the role of ECM viscoelasticity in fibrotic progression remains less understood. To examine how viscoelasticity affects the biophysical properties and regulates signaling of human mammary fibroblasts, we engineered elastic (E) and viscoelastic (VE) polyacrylamide hydrogels with comparable storage moduli (∼14.52 ± 1.03 kPa) but distinctly different loss moduli; mean loss moduli for VE gels was 36.9% higher at 0.05 Hz than E gels. Fibroblasts cultured on E hydrogels spread extensively (2428.93 ± 864.71 μm2), developed prominent stress fibers with higher zyxin intensity, and generated higher traction stresses (2931.57 ± 1732.61 Pa). In contrast, fibroblasts on VE substrates had 54.2% smaller focal adhesion areas, exhibited 51.8% lower critical adhesion strengths, and generated 21% lower traction stresses (p < 0.001). These substrates also promoted migration and showed enhanced proliferation with reduced Yes-associated protein (YAP) activity, suggesting a mechanotransduction shift that may involve alternative signaling pathways. In contrast, E substrates showed YAP nuclear translocation, consistent with greater cytoskeletal tension and contractility. These findings highlight the importance of energy dissipation mechanisms in regulating fibroblast function on substrates mimicking the fibrotic milieu. Our results demonstrate that tuning the ECM viscoelasticity is a useful strategy to regulate cell behaviors in tissue-engineered scaffolds and develop better disease modeling for regenerative medicine.

Syntheses of gold-manganese oxide nanocomposites were attempted by a redox-mediated growth method under varying mild reaction conditions with amino acid as a stabilization agent; finally, the nanocomposites were applied for superoxide dismutase (SOD)-mimic activity. Growth reaction was performed by the reduction of Au(III) with Mn(0) powder on the surface of citrate-stabilized gold nanoparticles as seeds. Variable reaction conditions were attempted to monitor the effect of the pH and, finally, optimized based on the critical properties of the nanocomposites including their long-term stability. In a neutral medium, tryptophan-stabilized Au-Mn3O4 nanocomposites were obtained. Stable Au-Mn2O3 nanocomposites were formed at basic pH in the presence of hydrophobic amino acids. The present work elucidates the role of amino acids, especially tryptophan, in stabilizing gold-manganese oxide nanocomposites. The effect of crystalline vs. the amorphous nature of Mn3O4 sheets in the tryptophan-stabilized nanocomposites was evaluated in SOD-mimetic applications. The IC50 values for the newly synthesized Au-Mn3O4 nanocomposites with crystalline or amorphous Mn3O4 sheets at room temperature were found to be 125 times and 25 times better with respect to the reported Mn3O4 nanoparticles synthesized after calcination at 600 °C. These results provide useful insights into the synthesis of gold-manganese oxide nanocomposites with tunable properties and their potential applications in the growing field of nanozymes.

Forces acting between an atomic force microscopy silicon nitride cantilever and the bacterial surface biopolymers of Escherichia coli or Pseudomonas putida were spatially probed in water. The interactions were fitted to a model of steric repulsion to estimate the bacterial surface biopolymer brush length and grafting density. The forces were further fitted to a Hertz model of contact mechanics modified by Sneddon et al. to quantify Young's modulus of elasticity for the cells. Contour plots of the quantified properties described above (i.e., the bacterial surface biopolymer brush length and grafting density, and Young's modulus of elasticity for the cells) based on the location coordinates on the bacterial surfaces were generated. Our contour plots indicated the bacterial cells organize their biopolymers uniquely to help them survive in the environment. Specifically, our results showed that the perimeter of a bacterial cell is characterized by a more flexible as well as longer biopolymer brush compared to those estimated at the center top of the cell. These results suggest that bacteria are likely to use their longer brushes on the edges to facilitate their adhesion by bridging surfaces. Also, they maintain their structural reinforcement by developing higher densities of grafted biopolymers and hence higher elasticities at their centers. Moreover, a stronger linear relationship was observed between the brush thicknesses and the grafting densities for the collapsed brush at the center of the cells when compared to the perimeter of the cells.

Orbital injuries or defects caused by various reasons are quite common, such as violent trauma or tumors. If the damaged orbits are not treated in a timely manner and the normal orbital structure cannot be restored, it may lead to ocular nerve injury, embedding or protrusion of orbital contents, and complications such as enophthalmos, diplopia, and eye movement disorders. Therefore, it is particularly important to repair orbital injuries or defects and reconstruct the normal structure of the orbit. Currently, there are various types of implants applied to reconstruct the orbit, which can be categorized as homogeneous and heterogeneous. Homogeneous materials are categorized as autologous and allogeneic, while heterogeneous materials are categorized into two main groups, absorbable and nonabsorbable materials. Ideal biomaterials for craniofacial fracture reconstruction must fulfill certain criteria such as biocompatibility, stability, safety, intraoperative adjustability, and low cost. This article provides a review of the advantages and shortcomings of various implants commonly used and the future direction of implant development.

Hepatoblastoma (HB) is a rare and aggressive pediatric liver tumor with complex etiology. Although necroptosis has been implicated in various cancers, its role in HB remains unclear. This study aimed to investigate the involvement of necroptosis-related genes and immune landscape in HB using integrative bioinformatics and machine learning approaches. Gene expression data from two independent HB datasets were integrated and analyzed. Differentially expressed genes (DEGs) and necroptosis-related DEGs (NR-DEGs) were identified, followed by functional enrichment analysis. Machine learning algorithms were employed to identify hub NR-DEGs. The immune landscape and hub NR-DEGs were investigated using single-sample gene set enrichment analysis (ssGSEA). A total of 1330 upregulated and 1061 downregulated common DEGs were identified. Five upregulated and fourteen downregulated NR-DEGs were identified, which were mainly enriched in immune-related pathways. Four hub NR-DEGs (SLC25A6, HSP90AB1, USP21, and CAMK2B) were identified as potential diagnostic biomarkers for HB. Immune infiltration analysis revealed elevated proportions of CD56bright natural killer cells and gamma delta T cells in HB patients, which significantly correlated with hub NR-DEG expression. ssGSEA indicated that hub NR-DEGs regulate various cellular processes, including cell cycle progression, RNA metabolism, protein synthesis, and viral infection response in HB. This study reveals the involvement of necroptosis-related genes and altered immune infiltration in HB pathogenesis, providing novel insights and potential therapeutic targets.

Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) imaging are established techniques for the imaging of biological samples. MALDI-MSI uses organic matrices to enhance desorption and ionization of biomolecules. Before analysis, the sample of interest must be coated with a matrix and the analytes must migrate into the matrix in order for molecular ion signals to be observed. The mechanisms involved in this migration and the sample handling procedures that influence this migration are not well understood. This leads to problems with reproducibility and accuracy of the images. In this study, ToF-SIMS was used to study the effects of exposure to mild ambient environmental conditions on migration of analytes in an α-Cyano-4-hydroxycinnamic acid (CHCA) matrix layer. A mouse brain section was coated with CHCA using an in-house built vapor deposition system and transferred to the ToF-SIMS instrument without breaking vacuum. The brain section was analyzed with ToF-SIMS immediately after vacuum transfer to the instrument, after 24 h storage in vacuum, and following a series of exposures to environmental conditions commonly observed in ambient laboratory air. The redistribution of lipids was observed to be dependent on the laboratory air humidity with minimal migration of most lipids below 50% relative humidity. Different migration behaviors were observed for different lipids as well as for different tissue types. The data show a complex multicomponent process of interdiffusion of the matrix and the brain lipids.

Present knowledge regarding manipulation of photon absorption cross-sectional areas of unicellular algal cells and its effect on bioproductivity is limited and cannot be applied to large-scale biomass production. Expecting that in the future such knowledge will come forward, this paper discusses the effect of manipulation of the photon absorption cross-sectional area of the PS II chlorophyll antenna on bioproductivity of flat-plate bioreactors under continuous illumination. A simple model for biomass generation in flat-plate bioreactors is developed. Two cross-sectional manipulation procedures aimed at optimizing reactor productivity are discussed: (1) finding an optimal constant cross-sectional area and (2) finding an optimal cross-sectional area profile that varies with depth in the reactor. It is well known that at low culture-density, photon exploitation efficiency is high at low photon flux densities (linear part of a biomass P-I curve) and diminishes in inverse proportion to flux density at high fluxes. Consequently, if instead of irradiating a given area of a low-culture density by a high photon flux density, the total flux is spread over a larger reactor surface-area at low flux densities, productivity per 1 m2 of reactor surface increases. Here, it is shown that the same idea also applies to high-culture density reactors and that the effect can be amplified significantly through judicious manipulation of the photon absorption cross-sectional area of the antenna. Compared to usual "natural" reactors (photon absorption cross sections are ≈1 nm2), bioproductivity of reactors operating under optimized photon absorption cross-sectional area may be 2-4 times higher.

Protein interactions on graphene-based materials (GBMs) are predominantly governed by interphase surface properties such as surface chemistry and roughness; however, the critical role of surface potential (SP) in modulating these interactions remains largely unexplored. In this work, we investigated a model study highlighting how two distinct GBMs [graphene oxide (GO) and reduced graphene oxide (RGO)] with different SP regulate protein interactions, spanning from macroscopic adsorption to molecular-level conformational changes. Through thermal reduction, hydrophilic GO was transformed into hydrophobic RGO, generating distinct SP of +120 mV for GO and +60 mV for RGO. This modulation in SP created a platform for differential protein interactions. The influence of SP on protein interactions was evident when fibronectin (FN) was introduced onto GO and RGO surfaces. Quartz crystal microbalance with dissipation and fluorescence microscopy revealed that the distinct SP of GO and RGO surfaces significantly affected FN adsorption. On the RGO substrate, which exhibited a lower SP, FN adsorption was ∼3 times greater than on the GO substrate. In contrast, FN on the GO adopted elongated fibrillar structures, driven by strong polar, hydrophilic, and electrostatic interactions at the molecular scale, regulating its conformation upon adsorption. Molecular docking simulations further supported these findings, indicating a stronger and more stable interaction between FN and RGO (binding energy C-score: -3.87, RMSD: 0.01 Å) than between FN and GO (C-score: -2.24, RMSD: 0.42 Å). Overall, this study underscores the pivotal role of SP of GBMs in modulating protein adsorption, binding stability, and conformational organization, providing key insights into the rational design of GBM biomaterials with tailored biointerface properties.

Magnetic nanoparticle-based targeted hyperthermia, combined with chemotherapy, is a promising approach for cancer treatment. In this study, a targeted magnetic drug delivery system was developed, comprising doxorubicin (DOX), a [D-Trp6] luteinizing hormone-releasing hormone (LHRH) (Triptorelin) ligand, and a polyethylene glycol (PEG)-coated magnetite core, aiming to enhance cancer therapy efficacy. Fourier-transform infrared spectroscopy confirmed the conjugation of LHRH onto the PEG-coated Fe3O4 nanoparticles. Ultraviolet-visible spectroscopy was employed to assess drug loading, revealing a loading efficiency of 66%. The DOX-loaded, LHRH-tagged PEG-coated Fe3O4 nanoparticles were evaluated for their cytotoxic effects on A549 and MCF-7 cancer cell lines under three treatment modalities: thermotherapy, chemotherapy, and combined thermo-chemotherapy, both with and without the application of a magnetic field. Cell viability was assessed using the 2,5-diphenyltetrazolium bromide (MTT) assay. In A549 cells, the combined thermo-chemotherapy treatment at a DOX concentration of 10 μg/ml resulted in an 88% reduction in cell viability, outperforming chemotherapy alone (62%) and thermotherapy alone (47%). Similarly, in MCF-7 cells, the combined treatment at 8 μg/ml DOX led to a 91% reduction in viability, surpassing the effects of chemotherapy (57%) and thermotherapy (45%) individually. Additionally, the targeted DOX-loaded nanoparticles significantly elevated interferon-gamma production, indicating an enhanced immune response and increased cancer cell apoptosis.