Journal of Membrane Biology最新文献

{"title":"Rapid Single-cell Measurement of Transient Transmembrane Water Flow under Osmotic Gradient.","authors":"Hong Jiang, Jinnawat Jongkhumkrong, Y J Chao, Qian Wang, Guiren Wang","doi":"10.1007/s00232-026-00375-6","DOIUrl":"10.1007/s00232-026-00375-6","url":null,"abstract":"<p><p>Aquaporins (AQPs) are critical for transmembrane water transport in response to osmotic gradients, but their gating and regulatory mechanisms remain poorly understood. A central challenge is the lack of methods to measure water flow across AQPs from individual cells with the spatiotemporal resolution and sensitivity equivalent to patch-clamp recordings of ion fluxes-a limitation stemming from the electrically silent nature of water flow. Here, we present a novel optical technique-Flow-Induced Fluorescence Increase Velocimetry (FIFIV) based on Laser-Induced Fluorescence Photobleaching Anemometry (LIFPA)-that enables direct, real-time monitoring of cytoplasmic flow induced by transmembrane water transport under osmotic pressure gradients. Using small molecular fluorescent dyes to label cytoplasm in single adherent MDA-MB-231 breast cancer cells, we show detection of instantaneous extremely low transmembrane water flow signals on the order of 1 μm/s following localized hypotonic stimulation. This approach circumvents the limitations of traditional volume-based osmotic permeability assays, achieving single-cell sensitivity and temporal resolution comparable to electrophysiological measurements of ion flux. FIFIV potentially provides a new optical approach for probing transmembrane water-flow-induced intracellular dynamics, and a foundation for future investigations of AQP regulation and gating mechanisms in physiopathological studies and drug discovery.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12935827/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147286162","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":"Oxysterol Induced Fluid-Fluid Phase Separation in Saturated Phosphatidylcholine Membranes: Influence of Lipid Chain Length.","authors":"P K Shabeeb, Sreeja Sasidharan, S Madhukar, Md Arif Kamal, V A Raghunathan","doi":"10.1007/s00232-026-00374-7","DOIUrl":"10.1007/s00232-026-00374-7","url":null,"abstract":"<p><p>We have recently reported the observation of closed-loop fluid-fluid immiscibility in 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid membranes containing either 25-hydroxycholesterol (25HCH) or 27-hydroxycholesterol (27HCH) (Kamal et al. Proc Natl Acad Sci 120(25):2216002120, https://doi.org/10.1073/pnas.2216002120 ,  2023). Here we extend these studies to membranes of symmetric, saturated phospholipids having chain length varying from 12 to 16 carbon atoms. The phase behavior of the PC-25HCH and PC-27HCH membranes were probed by using fluorescence microscopy, atomic force microscopy and small angle X-ray scattering. 25HCH is found to induce fluid-fluid coexistence in these membranes for lipid chains lengths varying from 12 to 15 C atoms, whereas 27HCH induces similar phase behavior for chain lengths varying from 13 to 16. Thus the occurrence of fluid-fluid coexistence in these membranes depends both on the position of the -OH group in the oxysterol side chain as well as the membrane thickness. Our earlier studies have indicated that the phase behavior of these binary membranes can be understood in terms of the temperature-dependent orientation of the oxysterol in the membrane. Our present results suggest that the relative energies of these orientations depend on the membrane thickness and the oxysterol structure. Observation of fluid-fluid immiscibility in different saturated lipid model membranes containing 25HCH or 27HCH shows the generic nature of this phase behavior.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"5"},"PeriodicalIF":2.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127347","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":"Membrane Remodeling Activity of Dengue Virus NS4A and NS1 Proteins: A Computational Perspective.","authors":"Dwaipayan Chaudhuri, Kalyan Giri","doi":"10.1007/s00232-025-00369-w","DOIUrl":"10.1007/s00232-025-00369-w","url":null,"abstract":"<p><p>Dengue virus (DENV) non-structural protein NS4A and NS1 are crucial for viral replication and have the ability to cause extensive remodeling of the host cell membrane. Here, a computational strategy has been used to study the structural and functional aspects of NS4A and NS1 in membrane interaction and remodeling. By employing multiscale all atom and coarse grained molecular dynamics simulations, we investigated the conformational dynamics of NS4A and NS1 and their interactions with model lipid bilayers. Our results establish that NS4A inserts preferentially into membranes in its native state as an integral membrane protein and causes curvature aided by its oligomerization event, which is in agreement with its proposed function in replication complex formation. NS1 has stable lipid-binding domains that can anchor and induce membrane curvature or stabilize remodelled membrane structures and perform its function as a peripherally bound membrane protein. These findings give molecular-level insights into the mechanism of how DENV hijacks host membranes for replication and identify potential targets for antiviral interventions. This study also plays an important role in updating our knowledge of flaviviral manipulation of membranes.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"6"},"PeriodicalIF":2.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127330","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":"Analysis of the Effect of the Magnetic Field on Water Flux Through TIP3;1 Aquaporins Using Molecular Dynamics in GROMACS.","authors":"Diego Fernando Nieto-Giraldo, José Mauricio Rodas Rodríguez, Javier Torres-Osorio","doi":"10.1007/s00232-025-00368-x","DOIUrl":"10.1007/s00232-025-00368-x","url":null,"abstract":"<p><p>Magnetobiology studies the effects of magnetic fields on biological systems. In this context, the Magnetobiology Research Group at the University of Caldas has hypothesized that magnetic treatment may influence water flow through cell membranes. To contribute to evaluating this hypothesis, this study analyzes the effect of magnetic fields on water transport through TIP3;1 aquaporins of Zea mays L. Molecular dynamics simulations were performed using a modified version of GROMACS that includes magnetic forces in the Velocity-Verlet algorithm, exposing a TIP3;1 homotetramer embedded in a lipid bilayer to static, uniform magnetic flux densities (B) ranging from 0 to 10 T and oriented along the membrane normal (z-axis). The system was solvated with the SPC/E water model. To assess the impact on water flow, we analyzed the conformational dynamics of TIP3;1, protein-water interactions within the single-file channel, and the osmotic permeability coefficient (p_f). Trajectory analysis revealed that the magnetic field alters the average pore radius and increases protein conformational variability. These structural changes affect the intermolecular interactions between the protein and water molecules, influencing water mobility through the channel. Systems exposed to magnetic fields showed up to a threefold increase in pf compared to the control. These findings suggest that magnetic fields can modulate water flow through membranes, supporting a possible mechanism of magnetically influenced water transport in biological systems.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"7"},"PeriodicalIF":2.6,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12876521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127325","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":"Targeting hORAI1-Mediated Calcium Influx in Triple-Negative Breast Cancer: A Computational Drug Discovery Approach.","authors":"Sangavi Pandi, Hemavathy Nagarajan, Sneha Subramaniyan, Jeyakanthan Jeyaraman, Sampathkumar Ranganathan, Langeswaran Kulanthaivel","doi":"10.1007/s00232-025-00365-0","DOIUrl":"10.1007/s00232-025-00365-0","url":null,"abstract":"<p><p>Store-operated calcium entry (SOCE) is a crucial pathway that aids in restoring depleted calcium levels in the endoplasmic reticulum (ER), consequently regulating cellular calcium homeostasis. When calcium stores are low, two key proteins are activated: STIM1, which senses the calcium levels in the ER, and ORAI1, the pore-forming subunit of calcium release-activated calcium (CRAC) channels. ORAI1 is overexpressed in triple-negative breast cancer (TNBC) and regulates the transcription of genes that regulate cancer progression. The complete atomic structure of human ORAI1 (hORAI1) remains unknown, which poses a challenge for developing targeted therapies. This study modeled the closed state of hORAI1, identifying it as a potential target for disrupting calcium influx and oncogenic signaling in TNBC. A pharmacophore hypothesis derived from Mildronate analogues was utilized to screen the COCONUT database for small compounds that stabilize the closed state of hORAI1. Five promising compounds were identified: CNP0006530, CNP0006516, CNP0008628, CNP0002844, and CNP0004972. These compounds exhibited docking scores ranging from - 7.461 to - 5.393 kcal/mol and formed stable interactions with crucial residues, Glu106 and Asp110. This likely aids in stabilizing the closed conformation and inhibiting calcium influx. Molecular dynamics simulations have demonstrated the structural stability and compactness of the lead complexes. Furthermore, principal PCA/FEL analyses have validated their conformational stability within a membrane environment. These findings provide novel insights into the structural gating processes of hORAI1 and emphasize the therapeutic potential of small compounds that target its closed state to inhibit calcium-mediated carcinogenesis in TNBC.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"4"},"PeriodicalIF":2.6,"publicationDate":"2026-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146087819","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":"Na⁺ Uptake Triggered in Adrenal Chromaffin Cells by a 5-ns Electric Pulse is Facilitated by Ca²⁺ Influx Via an L-Type-Like Ca²⁺ Channel Independent of Changes in Membrane Potential.","authors":"Lisha Yang, Josette Zaklit, Thomas W Gould, Gale L Craviso, Normand Leblanc","doi":"10.1007/s00232-026-00370-x","DOIUrl":"10.1007/s00232-026-00370-x","url":null,"abstract":"<p><p>Whole-cell voltage patch clamp studies have shown that in bovine adrenal chromaffin cells held at -70 mV, a single 5-ns, 5 MV/m pulse activates a membrane conductance carried partially by Na⁺ through TRPC4/5 channels and the sodium leak channel (NALCN). Here we used fluorescence imaging with the Na⁺ indicator ING-2 to further investigate Na⁺ influx pathways. A 5-ns, 5 MV pulse elicited a tetrodotoxin-insensitive rise in ING-2 fluorescence that exhibited a similar electric field dependency and response to pulse-pair stimulation as the inward current. Increases in ING-2 fluorescence were partially inhibited by the NALCN inhibitor CP96345, the TRPC4/5 channel inhibitor M084, or the broad spectrum TRP channel inhibitor La³⁺, and fully blocked by the combination of these agents, suggesting involvement also of a La³⁺-sensitive Na⁺ pathway. Cholesterol depletion with methyl-β-cyclodextrin or PIP₂ synthesis inhibition with wortmannin also reduced the response. Full inhibition was achieved with the selective L-type voltage-gated Ca²⁺ channel (VGCC) inhibitors nitrendipine, verapamil, or diltiazem but not the broad-spectrum inhibitor Cd²⁺. Inhibitors of N- and P/Q-type VGCC had no effect. Fluorescence Ca²⁺ imaging in voltage-clamped GCaMP6f-expressing murine chromaffin cells held at -70 mV revealed a nitrendipine-sensitive, Cd²⁺-insensitive increase in intracellular Ca²⁺ that accompanied the inward current. These results provide evidence that nanoelectropulse-induced Na⁺ influx into chromaffin cells involves several Na⁺ influx pathways that are facilitated by Ca²⁺ influx via an L-type-like Ca²⁺ channel associated with cholesterol-rich membrane domains. Investigating such membrane effects is essential for developing nanosecond electric pulse technologies for stimulating and/or modulating excitable cells.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"3"},"PeriodicalIF":2.6,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013305","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":"Peptide-Assisted Membrane Permeabilization: Effects of Waveform Polarity, Inter-Monopulse Interval, and Surface Charge in Red Blood Cells and Planar Lipid Bilayers.","authors":"José Alexander Alvarez-Bustamante, Diego Ortiz-Mejía, Victor V Lemeshko","doi":"10.1007/s00232-025-00366-z","DOIUrl":"10.1007/s00232-025-00366-z","url":null,"abstract":"<p><p>Permeabilization of biomembranes by polycationic peptides is known to depend on the membrane potential, although the exact mechanism of this process is not yet completely defined, to be effectively controlled. We quantified peptide-assisted permeabilization of red blood cells (RBCs) using a custom system that delivered microsecond bipulses configured as bimonopolar (BMP; same polarity) or bipolar (BP; opposite polarity), varying the inter-monopulse interval ([Formula: see text]). In RBC suspensions, bulk light transmittance at 650 nm showed that BMP yielded higher permeabilization effect than BP at short [Formula: see text], whereas lengthening [Formula: see text] mitigated bipolar cancellation and increased BP responses. Membrane surface charge modulation by moderate concentrations of deoxycholate and spermine increased and decreased, respectively, membrane permeabilization effects of polycationic peptides. Complementary measurements in planar lipid bilayers (BLMs) under an applied command voltage ([Formula: see text]) with polarity alternation showed remarkable conduction at negative bias, essentially decreased in the presence of 1 mM Mg²⁺. Infrared thermometry over RBC suspension revealed modest heating (≈ 2.5-6 °C), equal for BMP and BP applications, indicating an electrical rather than thermal origin for waveform effects. Finally, the designed electroporation protocols allow controlled short-time permeabilization of cell membrane that might be useful for biotechnological applications and therapeutic delivery.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"2"},"PeriodicalIF":2.6,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145913680","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":"Integrative Multiscale Simulations Uncover the Mechanistic Principles Governing COPII Mediated Vesicle Formation.","authors":"Sanjoy Paul","doi":"10.1007/s00232-025-00367-y","DOIUrl":"10.1007/s00232-025-00367-y","url":null,"abstract":"","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":"259 1","pages":"1"},"PeriodicalIF":2.6,"publicationDate":"2025-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145812145","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":"Hypoxia Modulates Membrane Mechanics in Pancreatic Cancer.","authors":"Prema Kumari Agarwala, Shobhna Kapoor","doi":"10.1007/s00232-025-00358-z","DOIUrl":"10.1007/s00232-025-00358-z","url":null,"abstract":"<p><p>Aggressive cancer cells such as pancreatic cells exhibit an enhanced metastatic phenotype that involves cell migration and invasion. Cellular membrane deformation is a key process implicit in cell movement. This implicates a link between altered lipid metabolism during cancer progression and modulated membrane properties and hence associated functions. One of the key factors underlying the aggressiveness of pancreatic cancer is the presence of the highest percentage of hypoxia, which further adds to the lipid metabolic reprogramming. The subsequent effect of hypoxia-induced lipidome changes on membrane properties governing cell movement was investigated in this work using a combination of cell biology, microscopy, and spectroscopy. Our findings revealed that hypoxia induces distinct lipidome signatures in a cell-line-dependent fashion, which in turn differentially modulates the cell membrane stiffness. The correlation of cell stiffness with other membrane properties and the actin cytoskeleton shows a random correlation indicating that hypoxic stress distinctly regulates specific membrane attributes governing cellular functioning and should be consulted for the development of effective treatments for pancreatic cancer.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"461-472"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144876537","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":"Molecular Insights into Interactions between Ofloxacin and Ionic Micelles.","authors":"Saqib Rabbani, Areesha Maryam, Muhammad Sohail, Athar Yaseen Khan","doi":"10.1007/s00232-025-00357-0","DOIUrl":"10.1007/s00232-025-00357-0","url":null,"abstract":"<p><p>The growing antimicrobial resistance presents a challenge in developing new potent drugs, but this effort is hindered by a lack of information regarding how these new drugs would behave in biomembranes. Surfactants are considered mimetic models for biomembranes and can be used to study drug-membrane interactions. In this study, we used two well-known surfactants-cationic cetyltrimethylammonium bromide and anionic sodium dodecyl sulfate-as model membranes to investigate their interaction with the antimicrobial drug ofloxacin (OFL). These interactions were studied using volumetric and acoustic methods over the temperature range of 293.15-323.15 K to determine the apparent molar volume, isentropic compressibility, apparent molar compressibility, acoustic impedance, relative association, and intermolecular free length. Furthermore, UV-Vis spectroscopy and cyclic voltammetry were employed to evaluate the binding constants and free energies of the drug-surfactant systems. These results provide key molecular insights into the thermodynamics of OFL partitioning and its binding mechanisms with amphiphilic assemblies. Such mechanistic understanding is crucial for the rational design of antibiotic delivery systems, facilitating precise control over drug loading and release dynamics in surfactant-based formulations.</p>","PeriodicalId":50129,"journal":{"name":"Journal of Membrane Biology","volume":" ","pages":"519-531"},"PeriodicalIF":2.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144692248","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}