Search Results (77)

Anterior cruciate ligament (ACL) rupture causes joint instability and increases the risk of osteoarthritis due to the ligament’s limited healing capacity. Silk, particularly from Bombyx mori, combines high cytocompatibility with robust biomechanical properties. Its main components are fibroin and sericin, with the latter usually being removed to reduce immunogenicity and improve biocompatibility. Silk threads were processed either as raw silk (designated as “untreated”) or subjected to a patented degumming procedure (DE102021118652A1) to obtain purified silk. Both variants were used alone or in combination with poly(L-lactic acid-co-caprolactone) (P(LA-CL)) fibers, yielding four scaffold groups: untreated silk, purified silk, untreated silk/P(LA-CL), and purified silk/P(LA-CL). Three-layer scaffolds were fabricated using a zigzag embroidery pattern. Structural analysis revealed scaffold porosity of ≈38% for silk, ≈46% for purified silk, and up to ≈70% for scaffolds containing P(LA-CL). Uniaxial tensile testing showed that purified silk scaffolds achieved the highest maximum force at break (≈684 N), whereas elongation at maximum force was limited in the hybrid scaffolds—silk/P(LA-CL) ≈ 28% and p-silk/P(LA-CL) ≈ 32%—despite the high intrinsic extensibility of P(LA-CL). All scaffolds supported cell adhesion and showed no cytotoxicity. P-silk and p-silk/P(LA-CL) scaffolds exhibited the highest fibroblast adherence and pronounced paxillin expression, indicating strong cell–material interactions. Gene expression of ligament-related ECM components and connexin 43 was maintained across all groups. These results demonstrate that embroidered silk fibroin scaffolds provide a reproducible architecture with tunable porosity and mechanical properties, supporting fibroblast colonization and ligament-specific ECM expression. Such scaffolds represent promising candidates for ACL tissue engineering and future graft development. Full article

Cell membranes and the cytoskeleton play crucial roles in the regulation of cellular responses by mediating mechanical forces and physical stimuli from the microenvironment through their viscoelastic properties. Investigating these properties provides valuable insights into disease mechanisms and therapeutic strategies. Gold nanorods (GNRs), especially under irradiation, exhibit lethal effects against Leishmania parasites through plasmonic photothermal conversion. In this study, we focus on evaluating the effects of non-irradiated GNRs on macrophage properties to better understand their intrinsic interactions with cells and support the development of future phototherapy applications. Here, defocusing microscopy (DM), a quantitative phase microscopy technique, was used to analyze membrane fluctuations in macrophages ($M\varnothing s$) exposed to GNRs (average length of $43\pm 8 \mathrm{n}\mathrm{m}$ and diameter of $20\pm 4 \mathrm{n}\mathrm{m}$) and infected with Leishmania amazonensis. By quantifying membrane–cytoskeleton fluctuation from defocused images, we extracted viscoelastic parameters, including bending modulus ($k_c$) and viscosity ($\eta$), to characterize membrane behavior in detail. Our results show that infection increases both $k_c$ and $\eta$, while treatment at IC₅₀ reduces infection and selectively increases $k_c$ without affecting $\eta$. In healthy macrophages, exposure to GNRs resulted in a reduction in both parameters, indicative of increased membrane fluidity and cytoskeletal rearrangement. These findings provide new insights into the biomechanical effects of GNRs on macrophages and may enlighten the design of future phototherapeutic approaches. Full article

Mechanotransduction plays an essential role in the fate determination of alveolar cells within the pulmonary system by translating mechanical forces into intricate biochemical signals. This process exclusively governs differentiation, phenotypic stability, and maintenance of alveolar epithelial cell subtypes, primarily the alveolar AT1/AT2 cells. Perturbed mechanical tension proportionally impacts alveolar cell phenotypic identity and their functional characteristics. The fundamental influence of respiratory mechanics on alveolar cell lineage commitment and sustenance is undeniable. AT1 cells are recognized as principal mechanosensors within the alveolus, directly perceiving and responding to mechanical forces imposed by respiration through cell–matrix interactions. These mechanical forces instigate a profound reorganization of the actin cytoskeleton within cells, indispensable for signal transduction and perpetuation of their differentiated phenotype, orchestrated by integrins and cell adhesion molecule-mediated signaling. The dysregulated mechanotransduction in the pulmonary system intrinsically contributes to the etiology and progression of various diseases, exemplified by pulmonary fibrosis. This review systematically elucidates the profound impact of mechanotransduction on alveolar cell differentiation and fate sustenance and underscores how its dysregulation contributes to the initiation and perpetuation of lung diseases. Full article

Spindle orientation (SO) plays a critical role in tissue morphogenesis, homeostasis, and tumorigenesis by ensuring accurate division plane positioning in response to intrinsic and extrinsic cues. While SO has been extensively linked to cell shape sensing and cortical forces, the interplay between shape- and force-sensing mechanisms remains poorly understood. Here, we reveal that SO is governed by two parallel mechanisms that ensure redundancy and adaptability in diverse cellular environments. Using live-cell imaging of cultured cells, we demonstrate that the long prometaphase axis (LPA) is a superior predictor of SO compared to the long interphase axis, reflecting adhesive geometry and force distribution efficiently at prometaphase. Importantly, we uncover a pivotal role for focal adhesion kinase (FAK) in mediating cortical mechanosensing to regulate SO in cells undergoing complete metaphase rounding. We show that in cells with complete metaphase rounding, FAK-dependent force sensing aligns the spindle with the major force vector, ensuring accurate division. Conversely, in cells retaining shape anisotropy during mitosis, a FAK-independent shape-sensing mechanism drives SO. These findings highlight a dual regulatory system for SO, where shape sensing and force sensing operate in parallel to maintain division plane fidelity, shedding light on the mechanisms that enable cells to adapt to diverse physical and mechanical environments. Full article

Recent studies on myogenic satellite cells (SCs) in Duchenne muscular dystrophy (DMD) documented altered division capacities and impaired regeneration potential of SCs in DMD patients and animal models. It remains unknown, however, if SC-intrinsic effects trigger these deficiencies at pre-contractile stages of myogenesis rather than resulting from the pathologic environment. In this study, we isolated SCs from a porcine DMD model and age-matched wild-type (WT) piglets for comprehensive analysis. Using immunofluorescence, differentiation assays, traction force microscopy (TFM), RNA-seq, and label-free proteomic measurements, SCs behavior was characterized, and molecular changes were investigated. TFM revealed significantly higher average traction forces in DMD than WT SCs (90.4 ± 10.5 Pa vs. 66.9 ± 8.9 Pa; p = 0.0018). We identified 1390 differentially expressed genes and 1261 proteins with altered abundance in DMD vs. WT SCs. Dysregulated pathways uncovered by gene ontology (GO) enrichment analysis included sarcomere organization, focal adhesion, and response to hypoxia. Multi-omics factor analysis (MOFA) integrating transcriptomic and proteomic data, identified five factors accounting for the observed variance with an overall higher contribution of the transcriptomic data. Our findings suggest that SC impairments result from their inherent genetic abnormality rather than from environmental influences. The observed biological changes are intrinsic and not reactive to the pathological surrounding of DMD muscle. Full article

This study examines the intrinsic optical enhancements of carbon fiber-reinforced polymers (CFRPs) achieved through the integration of magnesium oxide (MgO) nanoparticles, as well as Mg/MgO and titanium dioxide (TiO₂) thin films onto carbon fibers. Integration was performed by quasi-continuous electrophoretic deposition (EPD) and physical vapor deposition (PVD), respectively. Employing a customized electrophoretic cell, EPD facilitated uniform MgO nanoparticle deposition onto unsized carbon fibers, ensuring stable nanoparticle dispersion and precise fiber coating. As a result, the fibers exhibited increased ultraviolet (UV) reflectance, largely attributed to the optical properties of the protective MgO layer. In parallel, PVD enabled the deposition of Mg/MgO and TiO₂ thin films with tailored thicknesses, providing precise control over key optical parameters such as reflectivity and interference effects. Mg/MgO coatings demonstrated high UV reflectivity, while TiO₂ layers, with their varying refractive indices, generated vibrant colors in the visible (Vis) range through thickness-dependent light interference. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) assessed the quality, thickness, and uniformity of these thin films, and UV/Vis spectroscopy confirmed the influence of deposition parameters on the resulting optical performance. Post-lamination analyses revealed that both EPD and PVD modifications significantly enhanced UV reflectivity and allowed for customizable color effects. This dual strategy underscores the potential of combining EPD and PVD to develop advanced CFRPs with superior UV resistance, decorative optical features, and improved environmental stability. Full article

The removal of surface residues from single-layer graphene (SLG), including poly(methyl methacrylate) (PMMA) polymers and Cl⁻ ions, during the transfer process remains a significant challenge with regard to preserving the intrinsic properties of SLG, with the process often leading to unintended doping and reduced electronic performance capabilities. This study presents a rapid and efficient surface treatment method that relies on an aqueous sodium nitrite (NaNO₂) solution to remove such contaminants effectively. The NaNO₂ solution rinse leverages reactive nitric oxide (NO) species to neutralize ionic contaminants (e.g., Cl⁻) and partially oxidize polymer residues in less than 10 min, thereby facilitating a more thorough final cleaning while preserving the intrinsic properties of graphene. Characterization techniques, including atomic force microscopy (AFM), Kelvin probe force microscopy (KPFM), and X-ray photoelectron spectroscopy (XPS), demonstrated substantial reductions in the levels of surface residues. The treatment restored the work function of the SLG to approximately 4.79 eV, close to that of pristine graphene (~4.5–4.8 eV), compared to the value of nearly 5.09 eV for conventional SLG samples treated with deionized (DI) water. Raman spectroscopy confirmed the reduced doping effects and improved structural integrity of the rinsed SLG. This effective rinsing process enhances the reproducibility and performance of SLG, enabling its integration into advanced electronic devices such as organic light-emitting diodes (OLEDs), photovoltaic (PV) cells, and transistors. Furthermore, the technique is broadly applicable to other two-dimensional (2D) materials, paving the way for next-generation (opto)electronic technologies. Full article

Despite the huge progress achieved in the optimization of perovskite solar cell (PSC) performance, stability remains a limiting factor for technological commercialization. Here, a study on the photovoltaic, structural and morphological stability of semi-transparent formamidinium lead bromide-based PSCs is presented. This work focuses on the positive role of 2D nanoscale layer passivation, induced by perovskite surface treatment with a mixture of iso-Pentylammonium chloride (ISO) and neo-Pentylammonium chloride (NEO). In situ X-ray diffraction (XRD) is applied in combination with atomic force microscopy (AFM), and the results are correlated to the devices’ photovoltaic performances. The superior power conversion efficiency and overall stability of the ISO-NEO system is evidenced, as compared to the un-passivated device, under illumination in air. Furthermore, the role of the ISO-NEO treatments in increasing the morpho-structural stability is clarified as follows: a bulk effect resulting in a protective role against the loss in crystallinity of the perovskite 3D phase (observed only for the un-passivated device) and an interface effect, being the observed 2D phase crystallinity loss spatially localized at the interface with the 3D phase where a higher concentration of defects is expected. Importantly, the complete stability of the device is achieved with the passivated ISO-NEO-encapsulated device, allowing us to exclude the intrinsic degradation effects. Full article

BC is the most commonly diagnosed cancer and the second leading cause of cancer death among women worldwide. Cellular stress is a condition that leads to disrupted homeostasis by extrinsic and intrinsic factors. Among other stressors, hypoxia is a driving force for breast cancer (BC) progression and a general hallmark of solid tumors. Thus, intratumoral hypoxia is an important determinant of invasion, metastasis, treatment failure, prognosis, and patient mortality. Acquisition of the epithelial–mesenchymal transition (EMT) phenotype is also a consequence of tumor hypoxia. The cellular response to hypoxia is mainly regulated by the hypoxia signaling pathway, governed by hypoxia-inducible factors (HIFs), mainly HIF1α. HIFs are a family of transcription factors (TFs), which induce the expression of target genes involved in cell survival and proliferation, metabolic reprogramming, angiogenesis, resisting apoptosis, invasion, and metastasis. HIF1α cooperates with a large number of other TFs. In this review, we focused on the crosstalk and cooperation between HIF1α and other TFs involved in the cellular response to hypoxia in BC. We identified a cluster of TFs, proposed as the HIF1α-TF interactome, that orchestrates the transcription of target genes involved in hypoxia, due to their post-translational modifications (PTMs), including phosphorylation/dephosphorylation, ubiquitination/deubiquitination, SUMOylation, hydroxylation, acetylation, S-nitrosylation, and palmitoylation. PTMs of these HIF1α-related TFs drive their stability and activity, degradation and turnover, and the bidirectional translocation between the cytoplasm or plasma membrane and nucleus of BC cells, as well as the transcription/activation of proteins encoded by oncogenes or inactivation of tumor suppressor target genes. Consequently, PTMs of TFs in the HIF1α interactome are crucial regulatory mechanisms that drive the cellular response to oxygen deprivation in BC cells. Full article

Overuse injury is a frequent diagnosis in occupational medicine and athletics. Using an established model of upper extremity overuse, we sought to characterize changes occurring in the forepaws and forelimbs of mature female rats (14–18 months of age). Thirty-three rats underwent a 4-week shaping period, before performing a high-repetition low-force (HRLF) task for 12 weeks, with the results being compared to 32 mature controls. HRLF animals showed a reduced grip strength versus controls. ELISAs carried out in the HRLF rats, versus controls, showed elevated levels of IL1-α in tendons, IL1-α and TNF-α in distal bones/entheses, and TNF-α, MIP1-α/CCL3, and CINC-2/CXCL-3 in serum, as well as IL-6 in forelimb muscles and tendons, and IL-10 in serum. HRLF rats had elevated collagen deposition in the forepaw intrinsic muscles (i.e., fibrosis), entheseal microdamage, and articular cartilage degradation versus the control rats. CD68/ED1+ osteoclasts and single-nucleated cells were elevated in distal forelimb metaphyses of the HRLF animals, versus controls. Declines in grip strength correlated with muscle fibrosis, entheseal microdamage, articular cartilage damage, distal bone/enthesis IL1-α, and serum IL-6. These data demonstrate inflammatory and persistent degradative changes in the forearm/forepaw tissues of mature female animals exposed to prolonged repetitive tasks, changes with clinical relevance to work-related overuse injuries in mature human females. Full article

Nonmelanoma skin cancer (NMSC) presents a significant challenge to global healthcare due to its rising incidence, prompting the search for innovative treatments to overcome the limitations of current therapies. Our study aims to explore the potential effects of the liquid blood concentrate platelet-rich fibrin (PRF) on basal cell carcinoma cells (BCCs) and squamous cell carcinoma cells (SCCs) in order to obtain results that may lead to new possible adjunctive therapies for managing localized skin cancers, particularly NMSC. Basal cell carcinoma (BCC) cells and squamous cell carcinoma (SCC) cells were indirectly treated with PRF generated via different relative centrifugation forces, namely high and low RCF PRF, for 7 days. PRF-treated cells were comparatively analyzed for cell viability, proliferation and cell cycle- and apoptosis-related gene expression. Analysis of MTS assay results revealed a significant decrease in cell viability in both BCC and SCC cells following PRF treatment for 7 days. Ki-67 staining showed a decreased percentage of Ki-67-positive cells in both BCC and SCC cells after 2 days of treatment compared to the control group. The downregulation of CCND1 gene expression in both cell types at 2 days along with the upregulation of p21 and p53 gene expression in SCC cells demonstrated the effect of PRF in inhibiting cell proliferation and inducing cell cycle arrest, especially during the initial phases of treatment. Increased expression of caspase-8 and caspase-9 was observed, indicating the activation of both extrinsic and intrinsic apoptotic pathways by PRF treatment. Although the exact immunomodulatory properties of PRF require further investigation, the results of our basic in vitro studies are promising and might provide a basis for future investigations of PRF as an adjunctive therapy for managing localized skin cancers, particularly NMSC. Full article

The gastrointestinal (GI) tract is an organ actively involved in mechanical processes, where it detects forces via a mechanosensation mechanism. Mechanosensation relies on specialized cells termed mechanoreceptors, which convert mechanical forces into electrochemical signals via mechanosensors. The mechanosensitive Piezo1 and Piezo2 are widely expressed in various mechanosensitive cells that respond to GI mechanical forces by altering transmembrane ionic currents, such as epithelial cells, enterochromaffin cells, and intrinsic and extrinsic enteric neurons. This review highlights recent research advances on mechanosensitive Piezo channels in GI physiology and pathology. Specifically, the latest insights on the role of Piezo channels in the intestinal barrier, GI motility, and intestinal mechanosensation are summarized. Additionally, an overview of Piezo channels in the pathogenesis of GI disorders, including irritable bowel syndrome, inflammatory bowel disease, and GI cancers, is provided. Overall, the presence of mechanosensitive Piezo channels offers a promising new perspective for the treatment of various GI disorders. Full article

This paper investigates the influence of constituent weight ratios on optical and electrical properties, with a particular focus on the intrinsic properties (such as electrical mobility) of ternary organic blends, highlighting the role of a third component. The study explores novel donor:acceptor1:acceptor2 (D:A₁:A₂) matrix blends with photovoltaic potential, systematically adjusting the ratio of the two acceptors in the mixtures, while keeping constant the donor:acceptor weight ratio (D:A = 1:1.4). Herein, depending on this adjustment, six different samples of 100–400 nm thickness are methodically characterized. Optical analysis demonstrates the spectral complementarity of the component materials and exposes the optimal weight ratio (D:A₁:A₂ = 1:1:0.4) for the highest optical absorption coefficient. Atomic force microscopy (AFM) analysis reveals improved and superior morphological attributes with the addition of the third component (fullerene). In terms of the electrical mobility of charge carriers, this study finds that the sample in which A₁ = A₂ has the greatest recorded value [${\mu }_{max}=1.41\times {10}^{-4}{\mathrm{cm}}^2/(\mathrm{Vs}$)]. This thorough study on ternary organic blends reveals the crucial relationship between acceptor ratios and the properties of the final blend, highlighting the critical function of the third component in influencing the intrinsic factors such as electrical mobility, offering valuable insights for the optimization of ternary organic solar cells. Full article

The intrinsic biomechanical properties of cancer cells remain poorly understood. To decipher whether cell stiffness modulation could increase melanoma cells’ invasive capacity, we performed both in vitro and in vivo experiments exploring cell stiffness by atomic force microscopy (AFM). We correlated stiffness properties with cell morphology adaptation and the molecular mechanisms underlying epithelial-to-mesenchymal (EMT)-like phenotype switching. We found that melanoma cell stiffness reduction was systematically associated with the acquisition of invasive properties in cutaneous melanoma cell lines, human skin reconstructs, and Medaka fish developing spontaneous MAP-kinase-induced melanomas. We observed a systematic correlation of stiffness modulation with cell morphological changes towards mesenchymal characteristic gains. We accordingly found that inducing melanoma EMT switching by overexpressing the ZEB1 transcription factor, a major regulator of melanoma cell plasticity, was sufficient to decrease cell stiffness and transcriptionally induce tetraspanin-8-mediated dermal invasion. Moreover, ZEB1 expression correlated with Tspan8 expression in patient melanoma lesions. Our data suggest that intrinsic cell stiffness could be a highly relevant marker for human cutaneous melanoma development. Full article

The formation and function of membrane-less organelles (MLOs) is one of the main driving forces in the molecular life of the cell. These processes are based on the separation of biopolymers into phases regulated by multiple specific and nonspecific inter- and intramolecular interactions. Among the realm of MLOs, a special place is taken by the promyelocytic leukemia nuclear bodies (PML-NBs or PML bodies), which are the intranuclear compartments involved in the regulation of cellular metabolism, transcription, the maintenance of genome stability, responses to viral infection, apoptosis, and tumor suppression. According to the accepted models, specific interactions, such as SUMO/SIM, the formation of disulfide bonds, etc., play a decisive role in the biogenesis of PML bodies. In this work, a number of bioinformatics approaches were used to study proteins found in the proteome of PML bodies for their tendency for spontaneous liquid–liquid phase separation (LLPS), which is usually caused by weak nonspecific interactions. A total of 205 proteins found in PML bodies have been identified. It has been suggested that UBC9, P53, HIPK2, and SUMO1 can be considered as the scaffold proteins of PML bodies. It was shown that more than half of the proteins in the analyzed proteome are capable of spontaneous LLPS, with 85% of the analyzed proteins being intrinsically disordered proteins (IDPs) and the remaining 15% being proteins with intrinsically disordered protein regions (IDPRs). About 44% of all proteins analyzed in this study contain SUMO binding sites and can potentially be SUMOylated. These data suggest that weak nonspecific interactions play a significantly larger role in the formation and biogenesis of PML bodies than previously expected. Full article