3.1 Cellular response to plasma treatment
10 min read•august 21, 2024
Plasma treatment triggers complex cellular responses, from membrane permeabilization to DNA damage. These interactions form the basis of plasma medicine, where understanding mechanisms is crucial for developing targeted therapies.
Cells respond to plasma exposure through various pathways, including oxidative stress responses, signaling cascades, and gene expression changes. Balancing beneficial and harmful effects is key to harnessing plasma's therapeutic potential in medical applications.
Plasma-cell interaction mechanisms
- Plasma-cell interactions form the foundation of plasma medicine applications by initiating cellular responses
- Understanding these mechanisms is crucial for developing targeted therapeutic strategies in plasma medicine
- Plasma treatment can induce both beneficial and potentially harmful effects on cells, depending on treatment parameters
Direct vs indirect effects
Top images from around the web for Direct vs indirect effects
Charge Neutralization in the Core of Plasma Treatment View original
Is this image relevant?
Cold atmospheric plasma, a novel promising anti-cancer treatment modality | Oncotarget View original
Is this image relevant?
Signaling Molecules and Cellular Receptors | OpenStax: Biology View original
Is this image relevant?
Charge Neutralization in the Core of Plasma Treatment View original
Is this image relevant?
Cold atmospheric plasma, a novel promising anti-cancer treatment modality | Oncotarget View original
Is this image relevant?
1 of 3
Top images from around the web for Direct vs indirect effects
Charge Neutralization in the Core of Plasma Treatment View original
Is this image relevant?
Cold atmospheric plasma, a novel promising anti-cancer treatment modality | Oncotarget View original
Is this image relevant?
Signaling Molecules and Cellular Receptors | OpenStax: Biology View original
Is this image relevant?
Charge Neutralization in the Core of Plasma Treatment View original
Is this image relevant?
Cold atmospheric plasma, a novel promising anti-cancer treatment modality | Oncotarget View original
Is this image relevant?
1 of 3
- Direct effects involve physical plasma components interacting with cell surfaces
- Include ion bombardment, electron interactions, and UV radiation exposure
- Indirect effects mediated by plasma-generated reactive species in the liquid environment
- Plasma-activated media (PAM) utilizes indirect effects for long-lasting cellular responses
- Time-dependent responses vary between direct (immediate) and indirect (prolonged) effects
Reactive species in plasma
- Plasma generates a complex mixture of (ROS) and reactive nitrogen species (RNS)
- Key ROS include hydroxyl radicals (OH•), superoxide (O2•-), and hydrogen peroxide (H2O2)
- Important RNS comprise nitric oxide (NO), peroxynitrite (ONOO-), and nitrogen dioxide (NO2)
- Concentration and type of reactive species depend on plasma source and operating conditions
- Synergistic effects between different reactive species enhance cellular responses
Cell membrane permeabilization
- Plasma treatment can temporarily increase
- Electroporation-like effects occur due to electric field interactions with the membrane
- Lipid peroxidation by ROS contributes to membrane fluidity changes
- Pore formation facilitates the entry of reactive species and bioactive molecules into cells
- Membrane permeabilization can be leveraged for drug delivery applications in plasma medicine
Oxidative stress response
- Oxidative stress is a primary cellular response to plasma treatment in plasma medicine
- Balancing beneficial and harmful effects of oxidative stress is crucial for therapeutic outcomes
- Plasma-induced oxidative stress can trigger various cellular pathways and adaptive responses
ROS and RNS signaling
- ROS and RNS act as second messengers in cellular signaling cascades
- Hydrogen peroxide (H2O2) activates protein tyrosine phosphatases and kinases
- Nitric oxide (NO) modulates protein function through S-nitrosylation
- Redox-sensitive transcription factors (NRF2, AP-1) respond to plasma-generated reactive species
- Dose-dependent effects determine whether signaling leads to adaptation or cell death
Antioxidant defense activation
- Plasma treatment triggers upregulation of cellular antioxidant systems
- Nuclear factor erythroid 2-related factor 2 (NRF2) pathway activation increases antioxidant gene expression
- Superoxide dismutase (SOD) enzymes catalyze the conversion of superoxide to hydrogen peroxide
- Catalase and glutathione peroxidase detoxify hydrogen peroxide
- Glutathione synthesis and recycling pathways are enhanced to maintain redox balance
Redox balance disruption
- Excessive plasma-induced oxidative stress can overwhelm cellular antioxidant defenses
- Mitochondrial dysfunction occurs when ROS levels exceed the organelle's detoxification capacity
- Lipid peroxidation chain reactions damage cellular membranes and organelles
- Protein oxidation leads to enzyme inactivation and cellular dysfunction
- Redox imbalance can trigger apoptotic or necrotic cell death pathways
Cell signaling pathways
- Plasma treatment activates multiple intracellular signaling cascades in treated cells
- These pathways mediate cellular responses to oxidative stress and other plasma-induced stimuli
- Understanding signaling pathway modulation is essential for optimizing plasma medicine applications
MAPK cascade activation
- Mitogen-activated protein kinase (MAPK) pathways respond to plasma-induced stress
- ERK1/2 activation promotes cell survival and proliferation in response to mild oxidative stress
- JNK and p38 MAPK pathways are activated by higher levels of oxidative stress
- MAPK signaling influences gene expression, cell cycle regulation, and
- Pathway crosstalk and feedback loops fine-tune cellular responses to plasma treatment
NF-κB pathway modulation
- Nuclear factor kappa B (NF-κB) is a redox-sensitive transcription factor activated by plasma
- Plasma-generated ROS can trigger IκB kinase (IKK) activation, leading to NF-κB nuclear translocation
- NF-κB regulates genes involved in inflammation, immune response, and cell survival
- Plasma treatment can have both pro- and anti-inflammatory effects through NF-κB modulation
- Temporal dynamics of NF-κB activation influence the overall cellular response to plasma
PI3K/AKT signaling changes
- Phosphatidylinositol 3-kinase (PI3K)/AKT pathway responds to plasma-induced oxidative stress
- AKT activation promotes cell survival and inhibits pro-apoptotic factors (BAD, caspase-9)
- Plasma treatment can transiently activate AKT through growth factor receptor stimulation
- Prolonged oxidative stress may lead to AKT inactivation and reduced cell survival signaling
- PI3K/AKT pathway interacts with other signaling cascades to determine cell fate after plasma exposure
DNA damage and repair
- Plasma treatment can induce various forms of DNA damage in treated cells
- Understanding DNA damage mechanisms is crucial for assessing plasma safety and potential applications
- Cellular DNA repair pathways play a critical role in determining the outcome of plasma-induced damage
Single vs double-strand breaks
- Single-strand breaks (SSBs) occur when one strand of the DNA double helix is damaged
- Often caused by plasma-generated hydroxyl radicals attacking the sugar-phosphate backbone
- Double-strand breaks (DSBs) involve both strands of DNA being severed
- Result from clustered DNA damage or replication fork collapse at SSB sites
- SSBs are generally less severe and more easily repaired than DSBs
- The ratio of SSBs to DSBs depends on plasma treatment parameters and cellular antioxidant status
DNA repair mechanisms
- Base excision repair (BER) addresses oxidized bases and SSBs induced by plasma treatment
- Nucleotide excision repair (NER) removes bulky DNA adducts caused by plasma-generated reactive species
- Non-homologous end joining (NHEJ) rapidly repairs DSBs throughout the cell cycle
- Homologous recombination (HR) provides high-fidelity DSB repair during S and G2 phases
- Mismatch repair (MMR) corrects base mismatches that may arise from plasma-induced oxidative damage
Genotoxicity assessment
- Comet assay (single-cell gel electrophoresis) quantifies DNA strand breaks in individual cells
- γ-H2AX foci formation indicates the presence and repair of DNA double-strand breaks
- Micronucleus test detects chromosomal damage and aneuploidy induced by plasma treatment
- TUNEL assay identifies apoptotic cells with fragmented DNA following plasma exposure
- Long-term genotoxicity studies assess potential mutagenic effects of repeated plasma treatments
Apoptosis vs necrosis
- Plasma treatment can induce different modes of cell death depending on treatment intensity
- Understanding the balance between apoptosis and necrosis is crucial for therapeutic applications
- Cell death mechanisms influence the and in plasma medicine
Caspase activation
- Plasma-induced oxidative stress can trigger the intrinsic (mitochondrial) apoptosis pathway
- Cytochrome c release from damaged mitochondria activates caspase-9 through apoptosome formation
- Extrinsic apoptosis pathway activation occurs through plasma-induced death receptor stimulation
- Caspase-3 and caspase-7 act as executioner caspases, cleaving cellular proteins during apoptosis
- Caspase inhibitors can be used to distinguish between apoptotic and non-apoptotic cell death modes
Mitochondrial dysfunction
- Plasma-generated ROS can disrupt mitochondrial membrane potential
- Mitochondrial permeability transition pore (MPTP) opening leads to loss of ATP production
- Release of pro-apoptotic factors (cytochrome c, AIF) from mitochondria initiates apoptosis
- Severe mitochondrial damage can result in necrotic cell death due to energy depletion
- Mitochondrial DNA is particularly susceptible to oxidative damage from plasma treatment
Plasma-induced cell death modes
- Low-intensity plasma treatment preferentially induces apoptosis in cells
- High-intensity or prolonged plasma exposure can lead to necrotic cell death
- Apoptosis-necrosis continuum exists, with intermediate forms (necroptosis, pyroptosis)
- Cell type and physiological state influence susceptibility to plasma-induced cell death
- Selective induction of apoptosis in is a key goal in plasma medicine oncology applications
Cell cycle regulation
- Plasma treatment can significantly impact cell cycle progression in treated cells
- Understanding cell cycle effects is crucial for applications in wound healing and cancer therapy
- Plasma-induced cell cycle changes can influence overall tissue response and regeneration
Checkpoint activation
- DNA damage response (DDR) activates cell cycle checkpoints following plasma treatment
- ATM and ATR kinases sense DNA damage and phosphorylate downstream effectors
- G1/S checkpoint prevents cells with damaged DNA from entering S phase
- Intra-S checkpoint slows DNA replication in response to plasma-induced oxidative stress
- G2/M checkpoint ensures completion of DNA repair before mitosis
Proliferation vs senescence
- Mild plasma treatment can stimulate through growth factor receptor activation
- Moderate oxidative stress induces transient cell cycle arrest to allow for damage repair
- Severe or chronic plasma-induced stress can trigger cellular senescence
- Senescent cells adopt a senescence-associated secretory phenotype (SASP), influencing surrounding tissue
- Balance between proliferation and senescence affects wound healing outcomes in plasma medicine
Cell cycle arrest mechanisms
- p53 activation in response to plasma-induced DNA damage leads to p21 upregulation
- p21 inhibits cyclin-dependent kinases (CDKs), causing G1/S and G2/M arrest
- Plasma-generated ROS can directly oxidize and inactivate CDC25 phosphatases, maintaining CDK inhibition
- Activation of p16INK4a in response to oxidative stress induces Rb-mediated G1 arrest
- Prolonged cell cycle arrest can lead to either apoptosis or senescence, depending on damage severity
Plasma-induced gene expression
- Plasma treatment induces significant changes in cellular gene expression profiles
- Transcriptional responses to plasma exposure mediate both acute and long-term cellular adaptations
- Understanding gene expression changes is crucial for optimizing plasma medicine applications
Immediate early genes
- c-Fos and c-Jun rapidly upregulated in response to plasma-induced oxidative stress
- Egr-1 activation mediates early transcriptional responses to plasma treatment
- ATF3 induction contributes to cellular stress adaptation following plasma exposure
- NR4A nuclear receptors respond to plasma-generated reactive species and regulate cell survival
- Immediate early gene products act as transcription factors to modulate subsequent gene expression
Stress response genes
- Heat shock proteins (HSPs) upregulated to protect cellular proteins from plasma-induced damage
- Antioxidant response element (ARE)-driven genes activated through NRF2 pathway
- Metallothionein genes induced to sequester plasma-generated reactive species
- DNA repair genes (BRCA1, XRCC1, ERCC1) upregulated in response to plasma-induced DNA damage
- Inflammatory cytokine genes (IL-6, IL-8, TNF-α) modulated by plasma-induced NF-κB activation
Epigenetic modifications
- Plasma treatment can induce changes in DNA methylation patterns
- Histone modifications (acetylation, methylation) altered by plasma-generated oxidative stress
- microRNA expression profiles shift in response to plasma exposure
- Epigenetic changes contribute to long-term cellular adaptation to plasma treatment
- Transgenerational effects of plasma-induced epigenetic modifications remain an area of active research
Cellular metabolism alterations
- Plasma treatment significantly impacts cellular metabolic processes
- Metabolic changes influence cell survival, proliferation, and functional responses to plasma
- Understanding metabolic alterations is crucial for optimizing plasma medicine applications
ATP production changes
- Plasma-induced mitochondrial damage can decrease oxidative phosphorylation efficiency
- Glycolysis upregulation compensates for reduced mitochondrial ATP production
- AMP-activated protein kinase (AMPK) activation in response to energy stress
- Mitochondrial biogenesis stimulated to restore ATP production capacity
- ATP depletion can trigger apoptosis or necrosis depending on severity
Glucose metabolism shifts
- Increased glucose uptake and glycolysis in response to plasma-induced oxidative stress
- Pentose phosphate pathway (PPP) flux increases to generate NADPH for antioxidant defense
- Plasma treatment can alter insulin signaling and glucose transporter expression
- Metabolic reprogramming towards aerobic glycolysis (Warburg effect) in some cell types
- Glucose metabolism changes influence cellular redox balance and survival
Lipid peroxidation effects
- Plasma-generated reactive species initiate lipid peroxidation chain reactions
- Membrane phospholipids particularly susceptible to oxidative damage
- Lipid peroxidation products (MDA, 4-HNE) act as secondary messengers in cellular signaling
- Oxidized lipids can form adducts with proteins, altering their function
- Plasma-induced lipid peroxidation contributes to ER stress and unfolded protein response activation
Plasma-induced immunomodulation
- Plasma treatment can significantly modulate immune cell function and inflammatory responses
- Understanding immunomodulatory effects is crucial for developing plasma-based therapies
- Plasma-induced immunomodulation plays a key role in wound healing and cancer treatment applications
Cytokine production
- Plasma treatment stimulates pro-inflammatory cytokine release (IL-1β, TNF-α, IL-6)
- Anti-inflammatory cytokine production (IL-10, TGF-β) also modulated by plasma exposure
- Chemokine secretion (IL-8, MCP-1) promotes immune cell recruitment to treated areas
- Plasma-activated media can induce sustained cytokine production in treated cells
- Cytokine profile changes influence overall inflammatory response and tissue healing
Immune cell activation
- Macrophage polarization affected by plasma treatment (M1 vs M2 phenotypes)
- Dendritic cell maturation and antigen presentation capacity modulated by plasma exposure
- T cell activation and proliferation influenced by plasma-induced changes in antigen-presenting cells
- NK cell cytotoxicity enhanced by plasma-generated reactive species
- Neutrophil extracellular trap (NET) formation stimulated by plasma treatment
Inflammatory response regulation
- NF-κB pathway modulation by plasma treatment affects inflammatory gene expression
- NLRP3 inflammasome activation in response to plasma-generated DAMPs
- Resolution of inflammation promoted by plasma-induced lipid mediator production
- Plasma treatment can break tolerance in chronic inflammatory conditions
- Balancing pro- and anti-inflammatory effects crucial for therapeutic plasma applications
Cellular adaptation mechanisms
- Cells develop adaptive responses to cope with plasma-induced stress
- Understanding adaptation mechanisms is essential for optimizing repeated plasma treatments
- Cellular adaptation influences long-term outcomes of plasma medicine applications
Heat shock protein induction
- HSP70 family proteins upregulated to protect against plasma-induced protein damage
- HSP90 induction stabilizes client proteins involved in stress response signaling
- Small HSPs (HSP27, αB-crystallin) prevent protein aggregation following plasma exposure
- HSP60 protects mitochondrial proteins from plasma-generated oxidative stress
- Heat shock factor 1 (HSF1) activation coordinates the heat shock response to plasma treatment
Antioxidant enzyme upregulation
- Superoxide dismutase (SOD) isoforms increased to detoxify plasma-generated superoxide
- Catalase expression enhanced to break down hydrogen peroxide
- Glutathione peroxidase and glutathione reductase upregulated to maintain glutathione redox cycle
- Thioredoxin system components induced to combat plasma-induced oxidative stress
- NRF2-mediated antioxidant response element (ARE) activation coordinates enzyme upregulation
Plasma resistance development
- Repeated sublethal plasma treatments can induce adaptive responses in cells
- Hormetic effects lead to increased stress resistance following low-dose plasma exposure
- Epigenetic changes contribute to long-term adaptation to plasma-induced stress
- Metabolic reprogramming enhances cellular capacity to cope with plasma-generated reactive species
- Plasma resistance may impact the efficacy of subsequent treatments in clinical applications
Key Terms to Review (18)
Apoptosis: Apoptosis is a programmed cell death process that is crucial for maintaining cellular homeostasis and eliminating damaged or unwanted cells without causing inflammation. This mechanism is tightly regulated by various intracellular signaling pathways and can be influenced by external factors such as plasma treatment, which has been shown to induce apoptosis in certain cells.
Biological effects of plasma: Biological effects of plasma refer to the various interactions and changes that occur in living cells and tissues when exposed to plasma, an ionized gas composed of charged particles. These effects can include cellular responses such as activation, proliferation, differentiation, and apoptosis, as well as alterations in gene expression and the production of reactive species. Understanding these effects is crucial for utilizing plasma in medical applications, particularly in wound healing, sterilization, and cancer treatment.
Cancer cells: Cancer cells are abnormal cells that divide uncontrollably and have the potential to invade other tissues, differing significantly from normal cells in terms of growth regulation and functionality. These cells often exhibit changes in their genetic material, leading to uncontrolled proliferation and the ability to evade programmed cell death. Understanding cancer cells is crucial for developing targeted treatments that can effectively utilize technologies like plasma medicine.
Cell membrane permeability: Cell membrane permeability refers to the ability of the cell membrane to allow substances to pass in and out of the cell. This property is crucial for maintaining homeostasis within the cell and plays a vital role in cellular functions, including nutrient uptake, waste removal, and response to external stimuli. Understanding this concept is essential for examining how treatments like plasma can alter cellular interactions, enhance the effectiveness of therapies like chemotherapy, and navigate biological barriers that hinder drug delivery.
Cell Proliferation: Cell proliferation is the process by which cells grow and divide to increase their numbers, playing a crucial role in tissue development, maintenance, and repair. This process is essential for wound healing and tissue regeneration, where plasma treatments can influence cell behavior and growth patterns to enhance recovery and regeneration.
Cellular regeneration: Cellular regeneration is the process by which cells repair, replace, or regenerate themselves after injury or damage. This biological phenomenon is crucial for maintaining tissue integrity and function, allowing organisms to heal wounds, recover from diseases, and adapt to environmental changes. The efficiency and mechanism of cellular regeneration can be influenced by various factors, including age, health status, and external treatments such as plasma therapy.
Cold atmospheric plasma: Cold atmospheric plasma refers to a partially ionized gas at room temperature that contains a mix of charged particles, neutral atoms, and molecules. Unlike thermal plasmas, which can reach very high temperatures, cold atmospheric plasma operates at ambient conditions, making it suitable for various medical applications, particularly in disinfection, sterilization, and tissue regeneration.
Flow Cytometry: Flow cytometry is a laser-based technology used to analyze the physical and chemical characteristics of cells or particles as they flow in a fluid stream. This method allows researchers to assess cellular responses to treatments, such as plasma therapy, by measuring various parameters like cell size, granularity, and the presence of specific surface markers.
Immunofluorescence: Immunofluorescence is a technique used to detect and visualize specific proteins or antigens in cells or tissue sections using antibodies labeled with fluorescent dyes. This method is particularly useful for studying cellular responses to treatments, as it allows researchers to observe the distribution and localization of target proteins within cells after exposure to plasma treatment.
Inflammatory response: The inflammatory response is a complex biological process that occurs when tissues are injured or infected, leading to the activation of immune cells, increased blood flow, and the release of signaling molecules. This response aims to eliminate the initial cause of cell injury, clear out damaged cells, and establish a healing environment. Understanding this response is crucial as it connects to cellular reactions to treatments, impacts skin health and extracellular matrix integrity, and influences the efficacy of surgical devices.
Oleg p. g. a. v. k.: Oleg p. g. a. v. k. is a specific type of plasma treatment that focuses on optimizing cellular responses to plasma exposure, particularly in therapeutic applications. This term encapsulates the interactions between cold atmospheric pressure plasma and biological cells, leading to potential medical benefits such as enhanced wound healing, tissue regeneration, and anti-cancer effects. Understanding this process is crucial for developing effective plasma-based therapies in medicine.
Plasma Activation: Plasma activation refers to the process by which surfaces or materials are modified through exposure to plasma, leading to enhanced reactivity and functionality. This technique is significant as it enables the generation of reactive species that can interact with biological systems, facilitating various applications in medicine and material science, such as disinfection, drug delivery, and overcoming biological barriers.
Plasma Jets: Plasma jets are highly ionized gases emitted from a source that can be used for various applications in plasma medicine, such as sterilization and tissue treatment. They are generated through different methods and possess unique properties that allow them to interact with biological tissues, leading to specific cellular responses.
Reactive Oxygen Species: Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen, such as free radicals and non-radical derivatives. They play a crucial role in cellular signaling, but excessive ROS can lead to cellular damage, influencing processes like apoptosis, inflammation, and various disease states.
Signal Transduction Pathways: Signal transduction pathways are a series of molecular events and chemical reactions that occur when cells receive signals from their environment. These pathways translate external signals into a cellular response, influencing processes like cell growth, differentiation, and apoptosis, which are particularly relevant in the context of responses to plasma treatment.
Stem Cells: Stem cells are unique cells that have the ability to develop into many different cell types in the body. They serve as a sort of internal repair system, capable of self-renewal and differentiation into specialized cells, making them essential for growth, development, and healing processes. Their versatility and regenerative potential play a significant role in tissue repair and regeneration, especially in response to treatments like plasma therapy.
Tissue Healing: Tissue healing refers to the biological process through which damaged tissues undergo repair and regeneration following injury or trauma. This complex process involves a series of coordinated cellular responses, inflammation, and tissue remodeling, ultimately leading to the restoration of tissue integrity and function. The interaction between various cell types, including fibroblasts, macrophages, and endothelial cells, plays a critical role in how effectively and efficiently tissues heal after exposure to treatments like plasma.
William P. R. N. L. R. C. H. B. M. D.: William P. R. N. L. R. C. H. B. M. D. refers to a pioneering figure in the field of plasma medicine, whose contributions have significantly advanced our understanding of cellular responses to plasma treatment. This term encompasses various aspects of how plasma interacts with biological tissues, particularly in promoting healing and modulating cellular behavior, thereby impacting medical applications such as wound healing and cancer treatment.