V. Zablotskii

Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations

Non-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses, and provide a basis for better controlled biomedical applications.

Spin reorientation transitions in Pt/Co/Pt films under low dose Ga+ ion irradiation

An elegant route for tuning the magnetic anisotropy of ultrathin Co films by Ga+ ion irradiation is presented. The magnetic anisotropy of a Pt/Co(2.6 nm)/Pt film is first changed from in-plane to out-of-plane by uniform low dose Ga+ ion irradiation at 30 keV. When increasing the dose, a second spin reorientation transition toward the sample plane is also evidenced. This could be a way to design magnetic nanowires with perpendicular anisotropy, embedded in an in-plane magnetized environment, either by irradiation through a mask or focused ion beam. Tentative explanations on the origin of these two successive spin reorientations are proposed.

How a High-Gradient Magnetic Field Could Affect Cell Life.

The biological effects of high-gradient magnetic fields (HGMFs) have steadily gained the increased attention of researchers from different disciplines, such as cell biology, cell therapy, targeted stem cell delivery and nanomedicine. We present a theoretical framework towards a fundamental understanding of the effects of HGMFs on intracellular processes, highlighting new directions for the study of living cell machinery: changing the probability of ion-channel on/off switching events by membrane magneto-mechanical stress, suppression of cell growth by magnetic pressure, magnetically induced cell division and cell reprograming, and forced migration of membrane receptor proteins. By deriving a generalized form for the Nernst equation, we find that a relatively small magnetic field (approximately 1 T) with a large gradient (up to 1 GT/m) can significantly change the membrane potential of the cell and thus have a significant impact on not only the properties and biological functionality of cells but also cell fate.

Drastic changes of the domain size in an ultrathin magnetic film

A general framework for the domain size in any ultrathin film with perpendicular magnetic anisotropy is here discussed. The domain structure is analyzed by using the classical theory taking into consideration the demagnetization field contribution to the domain wall energy. A sinusoidal model is considered to describe the domain structure while approaching, in two different cases, the monodomain state with in-plane magnetization. The first case is realized applying a large enough in-plane magnetic field. The second one is obtained by decreasing the perpendicular magnetic anisotropy, which is connected in many ultrathin systems with the increase of film thickness. A change in the domain size of several orders of magnitude is obtained while approaching the magnetization reorientation region. The minimal stripe domain period p=8πlex2/d is calculated from the sinusoidal model, where lex is the exchange length and d is the thickness of the film. The range of possible domain size changes in ultrathin films is p...

The interplay between biological and physical scenarios of bacterial death induced by non-thermal plasma.

Direct interactions of plasma matter with living cells and tissues can dramatically affect their functionality, initiating many important effects from cancer elimination to bacteria deactivation. However, the physical mechanisms and biochemical pathways underlying the effects of non-thermal plasma on bacteria and cell fate have still not been fully explored. Here, we report on the molecular mechanisms of non-thermal plasma-induced bacteria inactivation in both Gram-positive and Gram-negative strains. We demonstrate that depending on the exposure time plasma induces either direct physical destruction of bacteria or triggers programmed cell death (PCD) that exhibits characteristic features of apoptosis. The interplay between physical disruption and PCD is on the one hand driven by physical plasma parameters, and on the other hand by biological and physical properties of bacteria. The explored possibilities of the tuneable bacteria deactivation provide a basis for the development of advanced plasma-based therapies. To a great extent, our study opens new possibilities for controlled non-thermal plasma interactions with living systems.

Non-thermal plasma mills bacteria: Scanning electron microscopy observations

Non-thermal plasmas hold great promise for a variety of biomedical applications. To ensure safe clinical application of plasma, a rigorous analysis of plasma-induced effects on cell functions is required. Yet mechanisms of bacteria deactivation by non-thermal plasma remain largely unknown. We therefore analyzed the influence of low-temperature atmospheric plasma on Gram-positive and Gram-negative bacteria. Using scanning electron microscopy, we demonstrate that both Gram-positive and Gram-negative bacteria strains in a minute were completely destroyed by helium plasma. In contrast, mesenchymal stem cells (MSCs) were not affected by the same treatment. Furthermore, histopathological analysis of hematoxylin and eosin–stained rat skin sections from plasma–treated animals did not reveal any abnormalities in comparison to control ones. We discuss possible physical mechanisms leading to the shred of bacteria under non-thermal plasma irradiation. Our findings disclose how helium plasma destroys bacteria and demo...

Down-regulation of adipogenesis of mesenchymal stem cells by oscillating high-gradient magnetic fields and mechanical vibration

Nowadays, the focus in medicine on molecular genetics has resulted in a disregard for the physical basis of treatment even though many diseases originate from changes in cellular mechanics. Perturbations of the cellular nanomechanics promote pathologies, including cardiovascular disease and cancer. Furthermore, whilst the biological and therapeutic effects of magnetic fields are a well-established fact, to date the underlying mechanisms remain obscure. Here, we show that oscillating high-gradient magnetic field (HGMF) and mechanical vibration affect adipogenic differentiation of mesenchymal stem cells by the transmission of mechanical stress to the cell cytoskeleton, resulting in F-actin remodelling and subsequent down-regulation of adipogenic genes adiponectin, PPARγ, and AP2. Our findings propose an insight into the regulation of cellular nanomechanics, and provide a basis for better controlled down-regulation of stem cell adipogenesis by HGMF, which may facilitate the development of challenging therape...

Modulation of monocytic leukemia cell function and survival by high gradient magnetic fields and mathematical modeling studies.

The influence of spatially modulated high gradient magnetic fields on cellular functions of human THP-1 leukemia cells is studied. We demonstrate that arrays of high-gradient micrometer-sized magnets induce i) cell swelling, ii) prolonged increased ROS production, and iii) inhibit cell proliferation, and iv) elicit apoptosis of THP-1 monocytic leukemia cells in the absence of chemical or biological agents. Mathematical modeling indicates that mechanical stress exerted on the cells by high magnetic gradient forces is responsible for triggering cell swelling and formation of reactive oxygen species followed by apoptosis. We discuss physical aspects of controlling cell functions by focused magnetic gradient forces, i.e. by a noninvasive and nondestructive physical approach.

Non-thermal air plasma promotes the healing of acute skin wounds in rats

Non-thermal plasma (NTP) has nonspecific antibacterial effects, and can be applied as an effective tool for the treatment of chronic wounds and other skin pathologies. In this study we analysed the effect of NTP on the healing of the full-thickness acute skin wound model in rats. We utilised a single jet NTP system generating atmospheric pressure air plasma, with ion volume density 5 · 1017 m−3 and gas temperature 30–35 °C. The skin wounds were exposed to three daily plasma treatments for 1 or 2 minutes and were evaluated 3, 7 and 14 days after the wounding by histological and gene expression analysis. NTP treatment significantly enhanced epithelization and wound contraction on day 7 when compared to the untreated wounds. Macrophage infiltration into the wound area was not affected by the NTP treatment. Gene expression analysis did not indicate an increased inflammatory reaction or a disruption of the wound healing process; transient enhancement of inflammatory marker upregulation was found after NTP treatment on day 7. In summary, NTP treatment had improved the healing efficacy of acute skin wounds without noticeable side effects and concomitant activation of pro-inflammatory signalling. The obtained results highlight the favourability of plasma applications for wound therapy in clinics.

Life on magnets: stem cell networking on micro-magnet arrays.

Interactions between a micro-magnet array and living cells may guide the establishment of cell networks due to the cellular response to a magnetic field. To manipulate mesenchymal stem cells free of magnetic nanoparticles by a high magnetic field gradient, we used high quality micro-patterned NdFeB films around which the stray field’s value and direction drastically change across the cell body. Such micro-magnet arrays coated with parylene produce high magnetic field gradients that affect the cells in two main ways: i) causing cell migration and adherence to a covered magnetic surface and ii) elongating the cells in the directions parallel to the edges of the micro-magnet. To explain these effects, three putative mechanisms that incorporate both physical and biological factors influencing the cells are suggested. It is shown that the static high magnetic field gradient generated by the micro-magnet arrays are capable of assisting cell migration to those areas with the strongest magnetic field gradient, thereby allowing the build up of tunable interconnected stem cell networks, which is an elegant route for tissue engineering and regenerative medicine.