Hampering Effect of Cholesterol on the Permeation of Reactive Oxygen Species through Phospholipids Bilayer: Possible Explanation for Plasma Cancer Selectivity

Plasma Processes & Polymers

et al. 2018

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We perform computer simulations supported by experiments to investigate the oxidation of an important signaling protein, that is, human epidermal growth factor (hEGF), caused by cold atmospheric plasma (CAP) treatment. Specifically, we study the conformational changes of hEGF with different degrees of oxidation, to mimic short and long CAP treatment times. Our results indicate that the oxidized structures become more flexible, due to their conformational changes and breakage of the disulfide bonds, especially at higher oxidation degrees. MM/GBSA calculations reveal that an increasing oxidation level leads to a lower binding free energy of hEGF with its receptor. These results help to understand the fundamentals of the use of CAP for wound healing versus cancer treatment at short and longer treatment times.

Section: Introductionmentioning

confidence: 99%

Impact of plasma oxidation on structural features of human epidermal growth factor

Yusupov

Lackmann

Plasma Processes & Polymers

et al. 2018

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“…Specifically, we studied the effect of lipid oxidation on phosphatidylserine translocation across the plasma membrane, which plays a vital role in apoptosis signaling [12]. Furthermore, we investigated the ROS oxidation of the head groups and lipid tails in the membrane [13], the permeation of ROS across oxidized and non-oxidized membranes, including the synergistic effect of plasma oxidation and electric field [14], and the hampering effect of cholesterol [15,16]. In general, our investigations showed that oxidation of the membrane leads to an increase in its fluidity and permeability to ROS, thereby affecting the abovementioned processes.…”

Section: Introductionmentioning

confidence: 99%

Possible Mechanism of Glucose Uptake Enhanced by Cold Atmospheric Plasma: Atomic Scale Simulations

Yusupov

Bogaerts

2018

Plasma

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Cold atmospheric plasma (CAP) has shown its potential in biomedical applications, such as wound healing, cancer treatment and bacterial disinfection. Recent experiments have provided evidence that CAP can also enhance the intracellular uptake of glucose molecules which is important in diabetes therapy. In this respect, it is essential to understand the underlying mechanisms of intracellular glucose uptake induced by CAP, which is still unclear. Hence, in this study we try to elucidate the possible mechanism of glucose uptake by cells by performing computer simulations. Specifically, we study the transport of glucose molecules through native and oxidized membranes. Our simulation results show that the free energy barrier for the permeation of glucose molecules across the membrane decreases upon increasing the degree of oxidized lipids in the membrane. This indicates that the glucose permeation rate into cells increases when the CAP oxidation level in the cell membrane is increased.

“…A significant number of studies have been done to identify the type and spatio-temporal distribution of ROS produced by biomedical plasmas and the reader is referred to [9,37] for details. Although the ROS composition between plasma devices may vary, it has been shown that plasma-derived ROS can oxidize lipids in the cell membrane, reduce the membrane fluidity and favour pore formation [38][39][40], a topic thoroughly reviewed in [19]. The permeabilization of the cell membrane facilitates the access of ROS into the intracellular compartment, as well as the release of cell contents to the ECM, as observed in necrotic cells [41].…”

Section: Plasma-derived Ros Cell Death and The Ecmmentioning

confidence: 99%

Modifying the Tumour Microenvironment: Challenges and Future Perspectives for Anticancer Plasma Treatments

Privat-Maldonado

Bengtson

et al. 2019

Cancers

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Tumours are complex systems formed by cellular (malignant, immune, and endothelial cells, fibroblasts) and acellular components (extracellular matrix (ECM) constituents and secreted factors). A close interplay between these factors, collectively called the tumour microenvironment, is required to respond appropriately to external cues and to determine the treatment outcome. Cold plasma (here referred as ‘plasma’) is an emerging anticancer technology that generates a unique cocktail of reactive oxygen and nitrogen species to eliminate cancerous cells via multiple mechanisms of action. While plasma is currently regarded as a local therapy, it can also modulate the mechanisms of cell-to-cell and cell-to-ECM communication, which could facilitate the propagation of its effect in tissue and distant sites. However, it is still largely unknown how the physical interactions occurring between cells and/or the ECM in the tumour microenvironment affect the plasma therapy outcome. In this review, we discuss the effect of plasma on cell-to-cell and cell-to-ECM communication in the context of the tumour microenvironment and suggest new avenues of research to advance our knowledge in the field. Furthermore, we revise the relevant state-of-the-art in three-dimensional in vitro models that could be used to analyse cell-to-cell and cell-to-ECM communication and further strengthen our understanding of the effect of plasma in solid tumours.