{"title":"The Effect of Xenon on the Voltage‒Current Characteristics of Tethered Lipid Bilayers.","authors":"Hadeel Alobeedallah, Bruce Cornell, Hans Coster","doi":"10.1007/s00232-025-00346-3","DOIUrl":"10.1007/s00232-025-00346-3","url":null,"abstract":"<p><p>In this study, we describe the effect of the noble gas, xenon on the electrical properties of tethered lipid bilayer membranes, (tBLMs), including the effect of xenon on the activation energy for electrical conduction through the tBLM. Such studies benefit from the stability of a tethered membrane given the wide range of temperatures that are scanned and the time required for these measurements. The results indicate that xenon increases the activation energy for electrical conduction through bilayers and decreases the average pore size that dominates the electrical conductance of the lipid bilayers at low voltages. Xenon possesses a high affinity for lipid membranes and is a potent general anaesthetic. Its anaesthetic potency is possibly associated with its effects on proteins embedded in the lipid membranes.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"213-224"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081542/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144043296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Role of Ion Channels in Alzheimer's Disease Pathophysiology.","authors":"Ranjit Bhoi, Tuhina Mitra, Kallam Tejaswi, Vaishnav Manoj, Swagata Ghatak","doi":"10.1007/s00232-025-00341-8","DOIUrl":"10.1007/s00232-025-00341-8","url":null,"abstract":"<p><p>Ion channels play an integral role in the normal functioning of the brain. They regulate neuronal electrical properties like synaptic activity, generation of action potentials, maintenance of resting membrane potential and neuronal plasticity, and modulate the physiology of non-neuronal cells like astrocytes and microglia. Dysregulation of ionic homeostasis and channelopathies are associated with various neurological disorders, including Alzheimer's disease (AD). Several families of ion channels are associated with AD pathophysiology and progression. In this review, we outline the current research centered around ion channel dysregulation during AD and discuss briefly the possibility of using ion channels as therapeutic targets.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"187-212"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081594/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cholesterol Affects the Pore Formation and the Membrane-Membrane Interaction Induced by an Antimicrobial Peptide, NK-2, in Phospholipid Vesicles.","authors":"Surajit Das, Rajeev Jain, Kalyan Kumar Banerjee, Pabitra Maity, Krishnananda Chattopadhyay, Sanat Karmakar","doi":"10.1007/s00232-025-00347-2","DOIUrl":"10.1007/s00232-025-00347-2","url":null,"abstract":"<p><p>Antimicrobial peptides are part of the innate immune response and show their antimicrobial activity by forming pores, followed by disintegration of the membrane. Cholesterol in the membrane can affect the pore formation process, as cholesterol is known to alter the permeability and elastic properties of the membrane. The present research systematically explores the role of cholesterol in modulating the interaction of the antimicrobial peptide NK-2 with phospholipid membranes, as well as the processes of pore formation induced by NK-2 within the membrane. Large unilamellar vesicles (LUVs) and giant unilamellar vesicles (GUVs) made from DOPC-DOPG and Egg PC with varying cholesterol concentrations have been studied using a variety of experimental techniques. The present study revealed that both the magnitude of zeta potential and surface charge density diminished as cholesterol concentrations increased at an intermediate NK-2 concentration. The proliferation of the size distributions of LUVs containing cholesterol when exposed to NK-2 indicates the occurrence of vesicle aggregation. The phase contrast micrographs of GUVs as well as the calcein release experiments on LUVs show evidence of pores. Notably, the incorporation of cholesterol into the membrane was found to have a significant effect on both the permeability of the membrane and the kinetics of the pore formation process. This biophysical research contributes essential knowledge regarding the role of cholesterol in influencing the antimicrobial efficacy of the membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"237-252"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055243","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Cesar Millan-Pacheco, Iris N Serratos, Gerardo J Félix-Martínez, Gerardo Blancas-Flores, Alejandra Osorno, Rafael Godínez
{"title":"Cholesterol Concentration in Cell Membranes and its Impact on Receptor-Ligand Interaction: A Computational Study of ATP-Sensitive Potassium Channels and ATP Binding.","authors":"Cesar Millan-Pacheco, Iris N Serratos, Gerardo J Félix-Martínez, Gerardo Blancas-Flores, Alejandra Osorno, Rafael Godínez","doi":"10.1007/s00232-025-00345-4","DOIUrl":"10.1007/s00232-025-00345-4","url":null,"abstract":"<p><p>This work describes a computer study that looks at how different amounts of cholesterol (0%, 25%, and 50%) in cell membranes change the relationship between ATP and the K<sub>ATP</sub> channel. This could explain why pancreatic beta-cells secrete insulin differently. We use computer simulations of molecular dynamics, calculations of binding free energy, and an integrated oscillator model to look at the electrical activity of beta-cells. There is a need for this kind of multiscale approach right now because cholesterol plays a part in metabolic syndrome and early type 2 diabetes. Our results showed that the increase in cholesterol concentration in the cell membrane affects the electrostatic interactions between ATP and the K<sub>ATP</sub> channel, especially with charged residues in the binding site. Cholesterol can influence the properties of a membrane, including its local charge distribution near the channel. This affects the electrostatic environment around the ATP-binding site, increasing the affinity of ATP for the channel as our results indicated from 0 to 25 and 50% cholesterol (- 141 to - 113 kJ/mol, respectively). Simulating this change in the affinity to ATP of the K<sub>ATP</sub> channels in a model of the electrical activity of the pancreatic beta-cell indicates that even a minimal increase could produce hyperinsulism. The study answers an important research question about how the structure of the membrane affects the function of K<sub>ATP</sub> and, in turn, insulin releases a common feature of metabolic syndrome and early stages of type 2 diabetes.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"225-236"},"PeriodicalIF":2.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12081584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Functional and Physiological Implications of Oligopeptide Transporters: Potential Targets for Pharmacological Interventions.","authors":"Tapas Roy, Madhu Nath, Nabanita Halder, Rohit Saxena, Thirumurthy Velpandian","doi":"10.1007/s00232-025-00348-1","DOIUrl":"https://doi.org/10.1007/s00232-025-00348-1","url":null,"abstract":"<p><p>Peptide transporters are important plasma membrane proteins that facilitate the cellular uptake of di- and tripeptides in addition to various peptidomimetic drugs. The proton-coupled oligopeptide transporter (POT) family consists of mainly four transporter proteins, which include two H<sup>+</sup> -coupled oligopeptide transporters known as PEPT1 (SLC15A1) and PEPT2 (SLC15A2), along with two peptide/histidine transporters referred to as PHT1 (SLC15A4) and PHT2 (SLC15A3). These transporters play an important role in the drug delivery process in mammalian tissues. They are highly expressed in tissues such as the small intestine, kidney, liver, lung, and eye. PHT1 shows expression in immune cells, especially in B cells and plasmacytoid dendritic cells. The pathophysiological relevance of peptide transporters is emerging to be crucial in various disease conditions, e.g., PEPT1 plays a role in the physiopathology of the gastrointestinal system, particularly in IBD. Upregulated expression of peptide transporters has also been positively related to inflammatory responses. An increasing number of peptide-based drug therapies have been reported to have the potential for development of novel classes of drugs. For example, Carnosine (beta-alanyl-L-histidine) has been demonstrated to act as an antioxidant, antiglycating agent, and neuroprotector. It is transported by PEPT1 and PEPT2, facilitating its protective effects against oxidative stress in neurons and intestinal epithelial cells. Moreover, it has applications in the treatment of multidrug-resistant cancers and has been shown to improve glucose metabolism. This review gives an insight into the functional, physiological and pharmacological importance of proton-coupled oligopeptide transporter.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Schisandrin B Improves Mitochondrial Function and Inhibits HT22 Cell Apoptosis by Regulating Sirt3 Protein.","authors":"Fei Hu, Songlin Tong, Hongming Xu","doi":"10.1007/s00232-025-00340-9","DOIUrl":"10.1007/s00232-025-00340-9","url":null,"abstract":"<p><p>Neurological diseases refer to pathological changes that occur in the brain, spinal cord, and peripheral nerves. Their etiologies are complex, treatment outcomes are poor, and prognoses are unfavorable. Therefore, how to improve the treatment efficacy of neurological diseases is an urgent problem to be addressed in current clinical practice. Schisandrin B, a commonly used traditional Chinese medicine in clinical settings, has anti-tumor, anti-inflammatory, and wound-healing promoting effects. However, there are relatively few studies on its application in the treatment of neurological diseases. In this study, HT22 nerve cells were cultured, and an injury model was constructed by applying H<sub>2</sub>O<sub>2</sub> stimulation to explore the protective effect of Schisandrin B on these cells. The research results showed that compared with the H<sub>2</sub>O<sub>2</sub> group, Schisandrin B could significantly increase the viability (30.872%) and migration ability (42.756%) of HT22 cells, and inhibit the apoptosis of HT22 cells (22.817%). Further exploration of the mechanism revealed that Schisandrin B regulated the mitochondrial dynamic balance and membrane potential level of HT22 cells by upregulating the expression of Sirt3 protein, enhanced the mitochondrial energy metabolism (with an increase of 53.411% in ATP production), and maintained the integrity of the quantity and structure of mitochondria, ultimately exerting a protective effect on HT22 cells.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"123-133"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Virjinia Doltchinkova, Victoria Vitkova, Ognyan Petkov, Meglena Kitanova, Angelina Stoyanova-Ivanova, Siya Lozanova, Avgust Ivanov, Chavdar Roumenin
{"title":"Gamma-Aminobutyric Acid Action on Membrane and Electrical Properties of Synaptosomes and Model Lipid Bilayers.","authors":"Virjinia Doltchinkova, Victoria Vitkova, Ognyan Petkov, Meglena Kitanova, Angelina Stoyanova-Ivanova, Siya Lozanova, Avgust Ivanov, Chavdar Roumenin","doi":"10.1007/s00232-025-00339-2","DOIUrl":"10.1007/s00232-025-00339-2","url":null,"abstract":"<p><p>Dysfunction of the main inhibitory neurotransmitter gamma-aminobutyric acid (GABA) is the underlying reason behind many neurological disorders including Alzheimer's and Huntington's diseases, autism spectrum disorders, anxiety, depression, hypertension, and cardiovascular diseases, among others. Here, we address neurotransmitter-induced alterations of synaptosomal and model membrane electrical properties for elucidating membrane-related biophysical mechanisms of neurological disorders. We focus on membrane surface characteristics of the pinched off nerve endings synaptosomes, which for decades have been a powerful tool in neurobiology. Microelectrophoretic measurements of GABA-treated negatively charged synaptosomes from rat cerebral cortex reveal lower negative zeta potential as a result of reduced electrical charge on the membrane surface at (1-4 h) after isolation. Conversely, enhancement of the surface parameters of synaptosomes (17-22 h) post isolation is obtained due to additional negatively exposed groups on the surface of the vesicles. The electrical properties of bilayer lipid membranes are probed by electrochemical impedance spectroscopy, reporting as light increase of the membrane electrical capacitance in the presence of GABA, likely related to membrane thinning and dielectric permittivity alterations. The neurotransmitter inhibits sodium-potassium as well as the total ATPase activity and slightly enhances magnesium-ATPase of native synaptic membranes. At low (pM) GABA concentrations the activity of acetylcholinesterase (AChE) in synaptic membranes increases. AChE inhibition is reported at higher GABA concentrations. The relation between the surface electrical properties of cells and the enzymatic activity of brain ATPases and AChE, as examined here, are expected to be helpful in the elucidation of membrane-mediated molecular mechanisms relevant to neurological disorders and conditions.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"173-186"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dengue Virus Fusion Peptide Promotes Hemifusion Formation by Disordering the Interfacial Region of the Membrane.","authors":"Smruti Mishra, Hirak Chakraborty","doi":"10.1007/s00232-025-00336-5","DOIUrl":"10.1007/s00232-025-00336-5","url":null,"abstract":"<p><p>Membrane fusion is the first step in the infection process of the enveloped viruses. Enveloped viruses fuse either at the cell surface or enter the cell through endocytosis and transfer their internal genetic materials by fusing with the endosomal membrane at acidic pH. In this work, we have evaluated the effect of the Dengue virus fusion peptide (DENV FP) on the polyethylene glycol (PEG)-mediated lipid mixing of vesicles (hemifusion formation) at pH 5 and pH 7.4 with varying cholesterol concentrations. We have demonstrated that the DENV FP promotes hemifusion formation during the fusion of small unilamellar vesicles (SUVs) mainly at pH 5.0. Moreover, the fusion process demonstrates a strong correlation between fusogenicity and the amount of membrane cholesterol. We have further evaluated the partitioning ability of the peptide in three different membranes at pH 5.0 and pH 7.4. The fusogenic ability of the peptide at pH 5.0 is associated with the composition-dependent binding affinity of the peptide to the membrane. The depth-dependent fluorescence probes are used to evaluate membrane organization and dynamics utilizing steady-state and time-resolved fluorescence spectroscopic techniques. Our results show that the DENV FP promotes hemifusion formation by fluidizing the interfacial region of the membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"161-171"},"PeriodicalIF":2.3,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143015304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}