Yan Mi

Cell membrane rupture plays a pivotal role in drug delivery, physical tumor therapies, and cellular mechanobiology. Despite its importance, the quantitative mechanical mechanisms governing membrane failure remain poorly understood. A375 human melanoma cells were employed as a representative model to investigate membrane rupture behavior through the integration of atomic force microscopy (AFM) puncture experiments and finite element simulations. The AFM measurements yielded a membrane rupture force of 27.09 ± 0.446 nN, an indentation depth of 3.46 ± 0.429 μm, and a rupture energy of 16.77 ± 0.902 fJ. Based on these experimentally obtained parameters, a finite element model was developed to reproduce the stress evolution and failure process associated with membrane puncture. The predicted equivalent stress, equivalent strain, and strain energy density differed from the experimentally derived values by only 4.4%, 4.9%, and 8.1%, respectively, demonstrating good agreement between simulation and experiment. Comparative analyses of linear elastic, elastoplastic, and hyperelastic constitutive formulations further revealed that the hyperelastic model provided the most accurate representation of membrane puncture behavior. This finding highlights the dominant role of large deformation nonlinear mechanics in governing membrane failure during AFM puncture. Overall, the combined experimental and computational framework established in this work offers quantitative insights into the mechanics of cell membrane rupture and provides a useful platform for future investigations of membrane damage mechanisms and biomechanical modeling of living cells.

Developing efficient and safe cancer treatment strategies remains a major challenge in clinical practice. In this study, we propose a novel magnetic mechanical-thermal therapy (MMTT) strategy based on magnetic nanoparticles, designed to enhance antitumor efficacy through the synergistic effects of magnetic mechanical forces and magnetic hyperthermia. To achieve this, a dual-magnetic-field system with precisely controllable parameters—comprising alternating and pulsed magnetic field—was constructed, and Fe ₃ O ₄ nanoparticles were selected as the therapeutic medium for systematic in vitro and in vivo studies. In the in vitro experiments, magnetic fields of 0.5 T, 1.0 T, and 1.5 T were combined with thermal treatments at 37 °C, 40 °C, and 43 °C. The results showed that MMTT significantly reduced A375 cell viability to 26%, induced a higher proportion of apoptotic and necrotic cells, caused pronounced cytoskeletal disruption, and decreased cell migration ability to 22.7% of that observed in the control group. In the in vivo experiments, the combination of a 1.5 T magnetic field and a 43 °C hyperthermic treatment significantly inhibited tumor growth in mice, reducing tumor volume to 9.57% of that of the control group and extending the mean survival time by 2.8-fold. Histopathological analysis showed that MMTT markedly increased tumor cell apoptosis and necrosis, with a 1.8-fold increase in the TUNEL-positive rate compared with single treatments, while no noticeable damage was observed in normal tissues. Furthermore, MMTT downregulated the expression of epithelial–mesenchymal transition-related proteins (N-cadherin, Vimentin, and Fibronectin), suggesting suppression of tumor metastatic potential. This study proposes an efficient, precise, and safe MMTT strategy, offering a promising and practical approach for cancer treatment.

Magnetomechanical therapy (MMT), an emerging and promising physical modality for cancer treatment, holds significant potential in oncology. Nevertheless, the precise mechanisms underlying its cytotoxic effects and the specific cellular targets involved, particularly in the context of pulsed magnetic fields (PMFs), remain incompletely understood. In this study, we investigated the therapeutic efficacy of microsecond pulsed magnetic fields (μs-PMFs) combined with iron oxide nanoparticles (IONPs) in A375 melanoma cells. Cell apoptosis and necrosis were quantified using YO-PRO-1/propidium iodide (PI) double staining to evaluate both treatment effectiveness and the predominant mode of cell death. In addition, fluorescent labeling of the cytoskeleton, cell membrane, and lysosomes with specific fluorophores was performed to identify the primary cellular structures affected by magnetic forces during treatment. The results demonstrated that MMT significantly reduced A375 cell viability, achieving an overall cell death rate of 61.16%. Notably, necrosis was identified as the predominant mode of cell death, accounting for 52.38% of total cell mortality. Furthermore, the cell membrane, cytoskeleton, and lysosomes were determined to be major cellular targets of magnetomechanical disruption. These findings provide critical insights into the cellular mechanisms of μs-PMF induced MMT and support its continued development toward clinical translation as a novel anti-tumor strategy.

Non-contact pulsed magnetic field (PMF) can alter cell membrane permeability, offering a novel pathway for the transmembrane delivery of exogenous substances. However, the dose–response characteristics of the relevant parameters remain unclear, and in vitro validation in combination with chemotherapeutic agents is still lacking. To address this gap, this study systematically evaluated the effects of magnetic induction intensity and pulse width on cell membrane permeability using a self-built, adjustable PMF generator, and further investigated, in a molecular size-oriented manner, the enhancement of cytotoxicity for different chemotherapeutic agents. The results showed that, within the tested parameter ranges, the cell permeabilization rate increased exponentially with magnetic induction intensity and followed a sigmoidal trend with pulse width. Moreover, the cytotoxicity of the small-molecular-size meisoindigo was markedly enhanced under the PMF (up to a 4.52-fold increase), whereas the larger-molecular-size paclitaxel showed only minimal potentiation. This Letter not only elucidates the parameter–dose relationships governing PMF-induced cell permeabilization, but also, for the first time, demonstrates the feasibility of PMF-synergized drug potentiation guided by drug molecular size. Together, these findings provide important theoretical and experimental support for parameter optimization and for expanding the applications of noninvasive magnetic field-assisted chemotherapy.

As a non-contact physical intervention technique, pulsed magnetic field (PMF) has been shown to regulate cell membrane permeability. However, the underlying mechanism remains unclear, and their permeabilization efficiency is relatively low. Building on the advantages of magneto-mechanical regulation with magnetic nanoparticles, this study proposes combining PMF with magnetic nanoparticles. By leveraging magneto-mechanical force (MMF) as the central mechanism, the aim is to enhance cell permeabilization rate through optimization of the applied force magnitude. First, a theoretical analysis of the forces acting on magnetic nanoparticles was performed to guide particle parameter selection. Next, the effects of PMF alone and its combination with magnetic nanoparticles on cell membrane permeability were examined through in vitro experiments. Finally, fluorescence probes were used to investigate the biochemical mechanisms underlying cell permeabilization induced by both treatments. The permeabilization experiment results showed that the combined treatment significantly enhanced cell permeabilization. Compared to PMF treatment alone, the half-maximal effective dose decreased by 27.85%, and the rate of change in permeabilization rate increased by 49.7%. Fluorescence staining further revealed that, unlike the biochemical pathways activated by PMF treatment alone, the combined treatment caused multiple disruptions in cytoskeletal microfilaments, confirming that it induced cell permeabilization through a physical mechanism involving mechanical stress. This study leveraged the MMF generated by magnetic nanoparticles under PMF to regulate cell membrane permeability, providing a novel approach for precise control of cell membrane permeability based on physical parameters.

Epoxy resin composites are widely used as insulation support materials in the field of high-voltage power systems due to their excellent mechanical and electrical properties. However, prolonged exposure to non-uniform electric fields can lead to surface charge accumulation caused by localized high field strength, further distorting the external electric field and resulting in partial discharges or even surface flashovers. Atmospheric-pressure plasma jet has been proved to effectively improve the surface insulation performance of epoxy resin, but conventional uniform modification methods are difficult to take into account the insulation requirements of different field strength regions. In order to enhance the surface flashover voltage of epoxy resin under non-uniform electric fields, this study, based on the characteristics of the non-uniform electric field distribution, employed the pulsed discharge atmospheric pressure plasma jet technology and used tetraethyl orthosilicate as the precursor to achieve non-linear gradient silicon deposition on the surface of the epoxy resin. The physicochemical and electrical properties of the material surface were measured before and after modification. The results show that non-linear graded silicon deposition via plasma treatment covers the material surface with silicon-oxygen films of varying thicknesses, leading to a non-linear graded distribution in surface roughness, surface conductivity, and other parameters. Compared to the untreated group, the flashover voltage increased by 17%, 24%, and 30.6% for the uniform, linear graded, and non-linear graded treatment groups, respectively. Furthermore, the non-linear graded group exhibited an additional 5.5% improvement in flashover voltage over the linear graded group, demonstrating the best enhancement effect. This study provides a simple, efficient and controllable method for improving the surface flashover voltage of epoxy resin under non-uniform electric field. The non-linear graded design can better meet the actual operating conditions of insulating materials, which is of great significance for the enhancement of surface flashover voltage in insulating materials.

Modern power systems require better heat dissipation and thermal stability, but traditional low-filler composites cannot significantly enhance thermal conductivity. To address this issue, electric field induction technology orientation can efficiently orient boron nitride nanosheets (BNNSs), thereby improving the thermal conductivity of epoxy composites composed of BNNSs as the thermally conductive filler. In this study, an innovative approach employing a pulsed superimposed direct current (DC) electric field to synergistically induce filler orientation is used to construct efficient thermally conductive channels. The study found that the thermal conductivity of the composite prepared by superimposing an 8 kV/mm pulsed electric field on a 30 V/mm DC electric field is about 0.474 W/(m·K), which is 34.66% higher than that prepared by only a pulsed-induced field and 17.5% higher than the theoretical superposition value. Similarly, the composite prepared by superimposing a 4 kV/mm pulsed electric field on a 70 V/mm DC electric field increased to about 0.464 W/(m·K), which is 27.47% higher than that prepared by only a DC-induced field and 12.4% higher than the theoretical superposition value. These results indicate that the superimposed electric field treatment synergistically improves the thermal conductivity of the composite. Compared to other materials, composites prepared using the superimposed pulsed and DC electric field induction also exhibit superior thermal stability. This strategy effectively addresses the issue of material thermal aging caused by insufficient thermal conductivity, providing innovative ideas and a solid theoretical foundation for material design and thermal management.

The synergistic application of magnetic fields and iron oxide nanorod particles (IONPs) presents a novel therapeutic approach for inducing lysosome-dependent cell death (LDCL) via magneto-mechanical force (MMF). This study demonstrates the efficacy of decaying oscillating pulsed magnetic fields (DOPMFs) to propel IONPs to induce rapid tumor regression via lysosomal membrane permeabilization (LMP). The systematic evaluation of dose-dependent parameters revealed that DOPMF intensity and pulse number critically determine A375 melanoma cell viability reduction. Mechanistic investigations identified two hallmark biomarkers of LMP: increased cytosolic cathepsin B activity and downregulated LAMP-2 expression. Crucially, in vivo experiments using A375 melanoma-bearing mouse models corroborated the therapeutic potential of this approach, showing significant tumor growth inhibition without systemic toxicity or invasive procedures. Collectively, our findings demonstrate that MMF by IONPs under DOPMF stimulation exhibits significant efficacy in suppressing melanoma proliferation, offering a non-invasive, targeted approach for oncological intervention.

The electric field orientation method effectively promotes the orientation and arrangement of BN nanosheets, forming a thermal conduction network and enhancing the thermal conductivity of the composite material. In this study, microsecond pulsed electric field and direct current electric field were applied to induce the orientation and arrangement of BN nanosheets and improve the thermal conductivity of epoxy resin composites. Under a microsecond pulsed electric field of 50 Hz, 1.5 μs, and 8 kV/mm, the average orientation angle of BN nanosheets increased by 147.7%, and the thermal conductivity of the composite reached 0.352 W/(m·K), which is 1.84 times that of pure epoxy resin. In contrast, under a DC electric field of 70 V/mm, the average orientation angle of BN nanosheets increased by only 57.9%, while the thermal conductivity of the composite reached 0.364 W/(m·K), 1.91 times that of pure epoxy resin. The results indicate that the microsecond pulsed electric field primarily enhances the local orientation of the fillers to improve thermal conductivity, whereas the DC electric field mainly enhances the global arrangement of the fillers to achieve a similar effect. Additionally, thermogravimetric analysis and differential scanning calorimetry were conducted to evaluate the thermal properties of the composites. The results demonstrate that after BN nanosheets orientation and arrangement within the epoxy resin induced by both microsecond pulsed and DC electric fields, the composites exhibited a higher glass transition temperature and improved thermal stability. This study systematically explores the effects of microsecond pulsed and DC electric fields on filler orientation and arrangement, providing valuable insights for the fabrication of electric field-oriented composites.