Journal of Membrane Biology最新文献

{"title":"Hetero-Oligomeric Protein Pores for Single-Molecule Sensing.","authors":"Remya Satheesan, Asuma Janeena, Kozhinjampara R Mahendran","doi":"10.1007/s00232-024-00331-2","DOIUrl":"https://doi.org/10.1007/s00232-024-00331-2","url":null,"abstract":"<p><p>Protein nanopores are emerging as versatile single-molecule sensors with broad applications in DNA and protein sequencing. However, their narrow size restricts the range of detectable analytes, necessitating the development of advanced nanopores to broaden their applications in biotechnology. This review highlights a natural hetero-oligomeric porin, Nocardia farcinica porin AB (NfpAB), based on the Gram-positive mycolata, Nocardia farcinica. The pore comprises two subunits, NfpA and NfpB, that combine to form a stable structure with a unique pore geometry, asymmetrical shape, and charge distribution. Single-channel electrical recordings demonstrate that NfpAB forms stable, high-conductance channels suitable for sensing charged molecules, particularly cationic polypeptides and cyclic sugars. This pore offers advantages such as enhanced control over molecular interactions due to densely crowded charged residues, thus allowing the quantification of voltage-dependent translocation kinetics. Notably, NfpAB contains intrinsic cysteines in the pore lumen, providing an accessible site for thiol-based reactions and attachment of molecular adapters. We propose that such hetero-oligomeric pores will be effective for several applications in nanopore technology for biomolecular detection and sequencing.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142856535","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":"Interaction of an Oomycete Nep1-like Cytolysin with Natural and Plant Cell-Mimicking Membranes.","authors":"Tina Snoj, Tjaša Lukan, Kristina Gruden, Gregor Anderluh","doi":"10.1007/s00232-024-00330-3","DOIUrl":"https://doi.org/10.1007/s00232-024-00330-3","url":null,"abstract":"<p><p>Plants are attacked by various pathogens that secrete a variety of effectors to damage host cells and facilitate infection. One of the largest and so far understudied microbial protein families of effectors is necrosis- and ethylene-inducing peptide-1-like proteins (NLPs), which are involved in important plant diseases. Many NLPs act as cytolytic toxins that cause cell death and tissue necrosis by disrupting the plant's plasma membrane. Their mechanism of action is unique and leads to the formation of small, transient membrane ruptures. Here, we capture the interaction of the cytotoxic model NLP from the oomycete Pythium aphanidermatum, NLP_Pya, with plant cell-mimicking membranes of giant unilamellar vesicles (GUVs) and tobacco protoplasts using confocal fluorescence microscopy. We show that the permeabilization of GUVs by NLP_Pya is concentration- and time-dependent, confirm the small size of the pores by observing the inability of NLP_Pya monomers to pass through them, image the morphological changes of GUVs at higher concentrations of NLP_Pya and confirm its oligomerization on the membrane of GUVs. In addition, NLP_Pya bound to plasma membranes of protoplasts, which showed varying responses. Our results provide new insights into the interaction of NLP_Pya with model lipid membranes containing plant-derived sphingolipids.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142848053","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":"Effect of Triterpenoids Betulin and Betulinic Acid on Pulmonary Surfactant Membranes.","authors":"Cisem Altunayar-Unsalan, Ozan Unsalan","doi":"10.1007/s00232-024-00329-w","DOIUrl":"https://doi.org/10.1007/s00232-024-00329-w","url":null,"abstract":"<p><p>The purpose of this work is to examine how triterpenoids betulin (BE) and betulinic acid (BA) affect the thermotropic phase behaviour and bilayer packing in pulmonary surfactant membranes. Therefore, the interaction of these triterpenoids with dipalmitoylphosphatidylcholine (DPPC) bilayers is studied by differential scanning calorimetry (DSC), attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy, atomic force microscopy (AFM), field emission scanning electron microscopy (FE-SEM), and quantum chemical computations with density functional theory (DFT). From DSC data, the effects are more pronounced with BE compared to BA. At BE concentration of 20 mol%, the pretransition does not completely disappear and the lamellar phase transition broadens further. There are two indistinguishable peaks in the main phase transition, which may indicate the start of inhomogeneous mixing or phase separation in the gel phase. BA reduces the main transition temperature and almost completely eliminates the pretransition at concentrations of 1-10 mol%. Endotherms continue to have a symmetric, broad form that suggests perfect mixing. From ATR-FTIR data, both triterpenoids display the CH₂ antisymmetric stretching, C = O stretching, PO₂^- asymmetric stretching to higher wavenumber in DPPC system. These results indicate an increase in the lateral mobility and dehydration in the polar head group and glycerol-acyl chain interface of DPPC liposomes. From microscopic results, it is found that the addition of high concentration (20 mol%) of BE and BA into pure DPPC membranes, single and double planar layers are formed, and the size of the liposomes increases. According to computational studies, the O₁₃₁-H₂₀₆ OH group of BE and the P₂₄-O₂₆ head group of DPPC formed a hydrogen bonding of 1.805 Å between BE and DPPC in gas phase. This hydrogen bonding is observed between BA and DPPC via the P₂₄-O₂₆ head group of DPPC and the O₁₃₂-H₂₀₉ OH group of BA.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":""},"PeriodicalIF":2.3,"publicationDate":"2024-12-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792757","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":"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 (Ca²⁺), sodium (Na⁺), and potassium (K⁺)-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":" ","pages":"269-280"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","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":"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":"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":" ","pages":"281-305"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","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}

{"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":"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":" ","pages":"257-268"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","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":"Correlation Between Antimicrobial Structural Classes and Membrane Partitioning: Role of Emerging Lipid Packing Defects.","authors":"S V Sankaran, Roni Saiba, Samapan Sikdar, Satyavani Vemparala","doi":"10.1007/s00232-024-00318-z","DOIUrl":"10.1007/s00232-024-00318-z","url":null,"abstract":"<p><p>In this study, a combination of bioinformatics and molecular dynamics simulations is employed to investigate the partitioning behavior of different classes of antimicrobial peptides (AMPs) into model membranes. The main objective is to identify any correlations between the structural characteristics of AMPs and their membrane identification and early-stage partitioning mechanisms. The simulation results reveal distinct membrane interactions among the various structural classes of AMPs, particularly in relation to the generation and subsequent interaction with lipid packing defects. Notably, AMPs with a structure-less coil conformation generate a higher number of deep and shallow defects, which are larger in size compared to other classes of AMPs. AMPs with helical component demonstrated the deepest insertion into the membrane. On the other hand, AMPs with a significant percentage of beta sheets tend to adsorb onto the membrane surface, suggesting a potentially distinct partitioning mechanism attributed to their structural rigidity. These findings highlight the diverse membrane interactions and partitioning mechanisms exhibited by different structural classes of AMPs.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"307-321"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584508/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141735543","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":"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":"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":" ","pages":"365-376"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","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":"Early Events in β₂AR 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":"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. β₂AR, a pharmacologically relevant GPCR, is known to be targeted for the treatment of asthma and cardiovascular diseases. The activation of β₂AR 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 β₂AR 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 β₂AR 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 β₂AR 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 β₂AR dimers, thereby providing an insight into the oligomerization mechanism of GPCRs.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"323-344"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","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":"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":"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":" ","pages":"377-389"},"PeriodicalIF":2.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11584437/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}