{"title":"The Role of the Swollen State in Cell Proliferation.","authors":"Behor Eleazar Cohen","doi":"10.1007/s00232-024-00328-x","DOIUrl":"https://doi.org/10.1007/s00232-024-00328-x","url":null,"abstract":"<p><p>Cell swelling is known to be involved in various stages of the growth of plant cells and microorganisms but in mammalian cells how crucial a swollen state is for determining the fate of the cellular proliferation remains unclear. Recent evidence has increased our understanding of how the loss of the cell surface interactions with the extracellular matrix at early mitosis decreases the membrane tension triggering curvature changes in the plasma membrane and the activation of the sodium/hydrogen (Na +/H +) exchanger (NHE1) that drives osmotic swelling. Such a swollen state is temporary, but it is critical to alter essential membrane biophysical parameters that are required to activate Ca2 + channels and modulate the opening of K + channels involved in setting the membrane potential. A decreased membrane potential across the mitotic cell membrane enhances the clustering of Ras proteins involved in the Ca2 + and cytoskeleton-driven events that lead to cell rounding. Changes in the external mechanical and osmotic forces also have an impact on the lipid composition of the plasma membrane during mitosis.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559268","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}
Anwaar S Chaudary, Yanglin Guo, Yuri N Utkin, Maryam Barancheshmeh, Ruben K Dagda, Edward S Gasanoff
{"title":"Sphingomyelin Inhibits Hydrolytic Activity of Heterodimeric PLA<sub>2</sub> in Model Myelin Membranes: Pharmacological Relevance.","authors":"Anwaar S Chaudary, Yanglin Guo, Yuri N Utkin, Maryam Barancheshmeh, Ruben K Dagda, Edward S Gasanoff","doi":"10.1007/s00232-024-00327-y","DOIUrl":"https://doi.org/10.1007/s00232-024-00327-y","url":null,"abstract":"<p><p>In this work, the heterodimeric phospholipase A<sub>2</sub>, HDP-2, from viper venom was investigated for its hydrolytic activity in model myelin membranes as well as for its effects on intermembrane exchange of phospholipids (studied by phosphorescence quenching) and on phospholipid polymorphism (studied by <sup>1</sup>H-NMR spectroscopy) to understand the role of sphingomyelin (SM) in the demyelination of nerve fibers. By using well-validated in vitro approaches, we show that the presence of SM in model myelin membranes leads to a significant inhibition of the hydrolytic activity of HDP-2, decreased intermembrane phospholipid exchange, and reduced phospholipid polymorphism. Using AutoDock software, we show that the NH<sup>δ+</sup> group of the sphingosine backbone of SM binds to Tyr22(C=O<sub>pb</sub><sup>δ-</sup>) of HDP-2 via a hydrogen bond which keeps only the polar head of SM inside the HDP-2's active center and positions the sn-2 acyl ester bond away from the active center, thus making it unlikely to hydrolyze the alkyl chains at the sn-2 position. This observation strongly suggests that SM inhibits the catalytic activity of HDP-2 by blocking access to other phospholipids to the active center of the enzyme. Should this observation be verified in further studies, it would offer a tantalizing opportunity for developing effective pharmaceuticals to stop the demyelination of nerve fibers by aberrant PLA<sub>2</sub>s with overt activity - as observed in brain degenerative diseases - by inhibiting SM hydrolysis and/or facilitating SM synthesis in the myelin sheath membrane.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142512121","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}
K Aruna, Subhajit Pal, Ankita Khanna, Samarjit Bhattacharyya
{"title":"Postsynaptic Density Proteins and Their Role in the Trafficking of Group I Metabotropic Glutamate Receptors.","authors":"K Aruna, Subhajit Pal, Ankita Khanna, Samarjit Bhattacharyya","doi":"10.1007/s00232-024-00326-z","DOIUrl":"https://doi.org/10.1007/s00232-024-00326-z","url":null,"abstract":"<p><p>Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system that regulates multiple different forms of synaptic plasticity, including learning and memory. Glutamate transduces its signal by activating ionotropic glutamate receptors and metabotropic glutamate receptors (mGluRs). Group I mGluRs belong to the G protein-coupled receptor (GPCR) family. Regulation of cell surface expression and trafficking of the glutamate receptors represents an important mechanism that assures proper transmission of information at the synapses. There is growing evidence implicating dysregulated glutamate receptor trafficking in the pathophysiology of several neuropsychiatric disorders. The postsynaptic density (PSD) region consists of many specialized proteins which are assembled beneath the postsynaptic membrane of dendritic spines. Many of these proteins interact with group I mGluRs and have essential roles in group I mGluR-mediated synaptic function and plasticity. This review provides up-to-date information on the molecular determinants regulating cell surface expression and trafficking of group I mGluRs and discusses the role of few of these PSD proteins in these processes. As substantial evidences link mGluR dysfunction and maladaptive functioning of many PSD proteins to the pathophysiology of various neuropsychiatric disorders, understanding the role of the PSD proteins in group I mGluR trafficking may provide opportunities for the development of novel therapeutics in multiple neuropsychiatric disorders.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378534","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":"Voltage Gated Ion Channels and Sleep.","authors":"Yan Zhang, Jiawen Wu, Yuxian Zheng, Yangkun Xu, Ziqi Yu, Yong Ping","doi":"10.1007/s00232-024-00325-0","DOIUrl":"https://doi.org/10.1007/s00232-024-00325-0","url":null,"abstract":"<p><p>Ion channels are integral components of the nervous system, playing a pivotal role in shaping membrane potential, neuronal excitability, synaptic transmission and plasticity. Dysfunction in these channels, such as improper expression or localization, can lead to irregular neuronal excitability and synaptic communication, which may manifest as various behavioral abnormalities, including disrupted rest-activity cycles. Research has highlighted the significant impact of voltage gated ion channels on sleep parameters, influencing sleep latency, duration and waveforms. Furthermore, these ion channels have been implicated in the vulnerability to, and the pathogenesis of, several neurological and psychiatric disorders, including epilepsy, autism, schizophrenia, and Alzheimer's disease (AD). In this comprehensive review, we aim to provide a summary of the regulatory role of three predominant types of voltage-gated ion channels-calcium (Ca<sup>2+</sup>), sodium (Na<sup>+</sup>), and potassium (K<sup>+</sup>)-in sleep across species, from flies to mammals. We will also discuss the association of sleep disorders with various human diseases that may arise from the dysfunction of these ion channels, thereby underscoring the potential therapeutic benefits of targeting specific ion channel subtypes for sleep disturbance treatment.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142362434","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":"Early Events in β<sub>2</sub>AR Dimer Dynamics Mediated by Activation-Related Microswitches.","authors":"Aneesh Kotipalli, Shruti Koulgi, Vinod Jani, Uddhavesh Sonavane, Rajendra Joshi","doi":"10.1007/s00232-024-00324-1","DOIUrl":"https://doi.org/10.1007/s00232-024-00324-1","url":null,"abstract":"<p><p>G-Protein-Coupled Receptors (GPCRs) make up around 3-4% of the human genome and are the targets of one-third of FDA-approved drugs. GPCRs typically exist as monomers but also aggregate to form higher-order oligomers, including dimers. β<sub>2</sub>AR, a pharmacologically relevant GPCR, is known to be targeted for the treatment of asthma and cardiovascular diseases. The activation of β<sub>2</sub>AR at the dimer level remains under-explored. In the current study, molecular dynamics (MD) simulations have been performed to understand activation-related structural changes in β<sub>2</sub>AR at the dimer level. The transition from inactive to active and vice versa has been studied by starting the simulations in the apo, agonist-bound, and inverse agonist-bound β<sub>2</sub>AR dimers for PDB ID: 2RH1 and PDB ID: 3P0G, respectively. A cumulative total of around 21-μs simulations were performed. Residue-based distances, RMSD, and PCA calculations suggested that either of the one monomer attained activation-related features for the apo and agonist-bound β<sub>2</sub>AR dimers. The TM5 and TM6 helices within the two monomers were observed to be in significant variation in all the simulations. TM5 bulge and proximity of TM2 and TM7 helices may be contributing to one of the early events in activation. The dimeric interface between TM1 and helix 8 were observed to be well maintained in the apo and agonist-bound simulations. The presence of inverse agonists favored inactive features in both the monomers. These key features of activation known for monomers were observed to have an impact on β<sub>2</sub>AR dimers, thereby providing an insight into the oligomerization mechanism of GPCRs.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142141657","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":"Evolution of Bioelectric Membrane Potentials: Implications in Cancer Pathogenesis and Therapeutic Strategies.","authors":"Anju Shrivastava, Amit Kumar, Lalit Mohan Aggarwal, Satyajit Pradhan, Sunil Choudhary, Ashish Ashish, Keshav Kashyap, Shivani Mishra","doi":"10.1007/s00232-024-00323-2","DOIUrl":"https://doi.org/10.1007/s00232-024-00323-2","url":null,"abstract":"<p><p>Electrophysiology typically deals with the electrical properties of excitable cells like neurons and muscles. However, all other cells (non-excitable) also possess bioelectric membrane potentials for intracellular and extracellular communications. These membrane potentials are generated by different ions present in fluids available in and outside the cell, playing a vital role in communication and coordination between the cell and its organelles. Bioelectric membrane potential variations disturb cellular ionic homeostasis and are characteristic of many diseases, including cancers. A rapidly increasing interest has emerged in sorting out the electrophysiology of cancer cells. Compared to healthy cells, the distinct electrical properties exhibited by cancer cells offer a unique way of understanding cancer development, migration, and progression. Decoding the altered bioelectric signals influenced by fluctuating electric fields benefits understanding cancer more closely. While cancer research has predominantly focussed on genetic and molecular traits, the delicate area of electrophysiological characteristics has increasingly gained prominence. This review explores the historical exploration of electrophysiology in the context of cancer cells, shedding light on how alterations in bioelectric membrane potentials, mediated by ion channels and gap junctions, contribute to the pathophysiology of cancer.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142057161","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}
Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami
{"title":"Residues of TRPM8 at the Lipid-Water-Interface have Coevolved with Cholesterol Interaction and are Relevant for Diverse Health Disorders.","authors":"Deep Shikha, Ritesh Dalai, Shamit Kumar, Chandan Goswami","doi":"10.1007/s00232-024-00319-y","DOIUrl":"https://doi.org/10.1007/s00232-024-00319-y","url":null,"abstract":"<p><p>TRPM8 is a non-selective cation channel that is expressed in several tissues and cells and also has a unique property to be activated by low-temperature. In this work, we have analyzed the conservation of amino acids that are present in the lipid-water-interface (LWI) region of TRPM8, the region which experiences a microenvironment near the membrane surface. We demonstrate that the amino acids present in the LWI region are more conserved than the transmembrane or even full-length TRPM8, suggesting strong selection pressure in these residues. TRPM8 also has several conserved cholesterol-binding motifs where cholesterol can bind in different modes and energies. We suggest that mutations and/or physiological conditions can potentially alter these TRPM8-cholesterol complexes and can lead to physiological disorders or even apparently irreversible diseases such as cancer and neurodegeneration.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989402","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":"A Model for Reversible Electroporation to Deliver Drugs into Diseased Tissues.","authors":"Nilay Mondal, D C Dalal","doi":"10.1007/s00232-024-00321-4","DOIUrl":"https://doi.org/10.1007/s00232-024-00321-4","url":null,"abstract":"<p><p>Drug delivery through electroporation could be highly beneficial for the treatment of different types of diseased tissues within the human body. In this work, a mathematical model of reversible tissue electroporation is presented for injecting drug into the diseased cells. The model emphasizes the tissue boundary where the drug is injected as a point source. In addition, the effect of drug loss at tissue boundaries through extracellular space is studied elaborately. Multiple pulses are applied to deliver a sufficient amount of drug into the targeted cells. The set of differential equations that model the physical circumstances are solved numerically. This model obtains a mass transfer coefficient (MTC), in terms of pore fraction coefficient and drug permeability that controls the drug transport from extracellular to intracellular space. The drug penetration throughout the tissue is captured for the application of different pulses. The boundary effects on drug concentration are highlighted in this study. The advocated model is able to perform homogeneous drug transport into the cells so that the affected tissue is treated completely. This model can be applied to optimize clinical experiments by avoiding the lengthy and costly in vivo and in vitro experiments.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917921","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":"Feasibility Study for the Use of Gene Electrotransfer and Cell Electrofusion as a Single-Step Technique for the Generation of Activated Cancer Cell Vaccines.","authors":"Marko Ušaj, Mojca Pavlin, Maša Kandušer","doi":"10.1007/s00232-024-00320-5","DOIUrl":"https://doi.org/10.1007/s00232-024-00320-5","url":null,"abstract":"<p><p>Cell-based therapies hold great potential for cancer immunotherapy. This approach is based on manipulation of dendritic cells to activate immune system against specific cancer antigens. For the development of an effective cell vaccine platform, gene transfer, and cell fusion have been used for modification of dendritic or tumor cells to express immune (co)stimulatory signals and to load dendritic cells with tumor antigens. Both, gene transfer and cell fusion can be achieved by single technique, a cell membrane electroporation. The cell membrane exposed to external electric field becomes temporarily permeable, enabling introduction of genetic material, and also fusogenic, enabling the fusion of cells in the close contact. We tested the feasability of combining gene electrotransfer and electrofusion into a single-step technique and evaluated the effects of electroporation buffer, pulse parameters, and cell membrane fluidity for single or combined method of gene delivery or cell fusdion. We determined the percentage of fused cells expressing green fluorescence protein (GFP) in a murine cell model of melanoma B16F1, cell line used in our previous studies. Our results suggest that gene electrotransfer and cell electrofusion can be applied in a single step. The percentage of viable hybrid cells expressing GFP depends on electric pulse parameters and the composition of the electroporation buffer. Furthermore, our results suggest that cell membrane fluidity is not related to the efficiency of the gene electrotransfer and electrofusion. The protocol is compatible with microfluidic devices, however further optimization of electric pulse parameters and buffers is still needed.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141917922","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}
Pedro Alejandro Fong-Coronado, Verónica Ramirez, Verónica Quintero-Hernández, Daniel Balleza
{"title":"A Critical Review of Short Antimicrobial Peptides from Scorpion Venoms, Their Physicochemical Attributes, and Potential for the Development of New Drugs.","authors":"Pedro Alejandro Fong-Coronado, Verónica Ramirez, Verónica Quintero-Hernández, Daniel Balleza","doi":"10.1007/s00232-024-00315-2","DOIUrl":"10.1007/s00232-024-00315-2","url":null,"abstract":"<p><p>Scorpion venoms have proven to be excellent sources of antimicrobial agents. However, although many of them have been functionally characterized, they remain underutilized as pharmacological agents, despite their evident therapeutic potential. In this review, we discuss the physicochemical properties of short scorpion venom antimicrobial peptides (ssAMPs). Being generally short (13-25 aa) and amidated, their proven antimicrobial activity is generally explained by parameters such as their net charge, the hydrophobic moment, or the degree of helicity. However, for a complete understanding of their biological activities, also considering the properties of the target membranes is of great relevance. Here, with an extensive analysis of the physicochemical, structural, and thermodynamic parameters associated with these biomolecules, we propose a theoretical framework for the rational design of new antimicrobial drugs. Through a comparison of these physicochemical properties with the bioactivity of ssAMPs in pathogenic bacteria such as Staphylococcus aureus or Acinetobacter baumannii, it is evident that in addition to the net charge, the hydrophobic moment, electrostatic energy, or intrinsic flexibility are determining parameters to understand their performance. Although the correlation between these parameters is very complex, the consensus of our analysis suggests that there is a delicate balance between them and that modifying one affects the rest. Understanding the contribution of lipid composition to their bioactivities is also underestimated, which suggests that for each peptide, there is a physiological context to consider for the rational design of new drugs.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":null,"pages":null},"PeriodicalIF":2.3,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11289363/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141581410","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}