Biochimica et biophysica acta. Biomembranes最新文献

{"title":"Contribution to the special BBA issue dedicated to Joachim Seelig from lipid bilayers to the innate immune system","authors":"Anna Seelig","doi":"10.1016/j.bbamem.2025.184483","DOIUrl":"10.1016/j.bbamem.2025.184483","url":null,"abstract":"<div><div>This personal review in memory of Joachim Seelig covers half a century of membrane biophysics. The topics chosen give insight into the structure and function of our innate immune system, consisting in the membranes covering the external and internal body surfaces in contact with the outside world. Their core is the lipid bilayer in its liquid crystalline state. We investigated its average structure and fluidity by deuterium-nuclear magnetic resonance spectroscopy (D-NMR) using selectively deuterated lipids. Close to the lipid-water interface, lipids retain a defined average structure with the glycerol backbone oriented perpendicular to the membrane surface. The characteristic structure of lipids remains in the presence of transmembrane proteins and guarantees a tight membrane packing near the aqueous phases. The order of lipid segments remains approximately constant decreasing only towards the membrane center. Were cells surrounded by lipids only, hydrophobic molecules would nevertheless penetrate the membranes and reach the nucleus, the smaller ones more rapidly and the larger one more slowly. To protect cells from intruding mutagenic compounds, a significant number of defense proteins have evolved, including ATP binding cassette (ABC) transporters and pattern recognition receptors (PRR). Interestingly, the different defense proteins recognize compounds that carry specific hydrogen bond acceptor patterns and could interfere with DNA or RNA. ABC transporters and pattern recognition receptors remove them from the lipid bilayer before they reach the cytosol to prevent mutagenesis. While these proteins are well known to contribute to multidrug resistance (MDR), their significant role in innate immunity only starts to emerge.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184483"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transmembrane channel-like 4 (TMC4) could act as a negative regulator of KCNQ1 (Kv7.1) potassium channel","authors":"Hirota Aoyagi,&nbsp;Koya Kawaguchi,&nbsp;Saori Yano-Nashimoto,&nbsp;Soichiro Yamaguchi","doi":"10.1016/j.bbamem.2025.184460","DOIUrl":"10.1016/j.bbamem.2025.184460","url":null,"abstract":"<div><div>TMC4 is a member of the transmembrane channel-like (TMC) protein family. In this family, TMC1 and TMC2 are thought to form the mechano-electrical transduction (MET) channel in the inner ear. On the other hand, the intrinsic functions of the other TMC family members (TMC3-8) are largely unknown. KCNQ1 (Kv7.1) channel is a voltage-gated potassium channel and plays crucial physiological roles with its auxiliary subunits, KCNE proteins (e.g. KCNQ1/KCNE1 complex contributes to cardiac repolarization, and KCNQ1/KCNE3 complex participates in epithelial ion transport). Recently, it was reported that TMC1 and TMC2 interacted with KCNQ1 and suppressed its K⁺ currents. However, the relationships between KCNQ1 and the other TMC proteins have not been examined. Here, we show a novel interaction and a functional association between overexpressed TMC4 and KCNQ1. The Bead Halo assay and FRET analysis revealed the physical interaction between these two proteins. Whole-cell patch clamp recording demonstrated that co-expression of TMC4 reduced KCNQ1 current densities without altering their voltage dependence and activation kinetics. This effect was also observed in the KCNQ1/KCNE1 and KCNQ1/KCNE3 channel complexes. A structural prediction using AlphaFold-Multimer suggested possible interaction sites between TMC4 and KCNQ1. Mutageneses, followed by patch clamp recording, suggested that specific amino acid residues at these sites contribute to the inhibitory effect of TMC4. These results indicate that TMC4 could function as a negative regulator of the KCNQ1 channel. Our findings could enhance the understanding of KCNQ1 channel regulation and propose potential research directions on the function of TMC4 under various physiological and pathological conditions.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184460"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228384","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Designing biologically-relevant cell membrane models with natural lipid mixtures","authors":"Krishna Chaithanya Batchu ,&nbsp;Giacomo Corucci ,&nbsp;Valérie Laux ,&nbsp;Frank Gabel ,&nbsp;Giovanna Fragneto ,&nbsp;Alessandra Luchini","doi":"10.1016/j.bbamem.2025.184474","DOIUrl":"10.1016/j.bbamem.2025.184474","url":null,"abstract":"<div><div>Cell membranes provide vital biological functions by separating the cell components from the surrounding environment and providing a bioactive interface for several biological processes. The direct extraction of intact cell membranes and their investigation with biophysical methods is heavily limited by their compositional complexity and intrinsic fragility. Therefore, over the years, membrane models including vesicles, lipid monolayers, supported lipid bilayers and lipid multilayers, were suggested as alternatives to study the physico-chemical properties of cell membranes. These membrane models are typically produced with 1-3 synthetic lipid species and their application is therefore restricted by their composition, being too simple as compared to native cell membranes.</div><div>In this review, we discuss the latest efforts towards producing more biologically relevant membrane models by utilizing natural lipid extracts. These are produced by extracting and purifying lipids expressed by different types of microbial cells. In part I, we present a detailed discussion of the methods currently available for obtaining the extracts, and in part II, we discuss how to use them for preparing cell membrane models and characterizing their structure. The majority of the discussed studies refer to <em>Escherichia coli</em> and <em>Pichia pastoris</em> glycerophospholipid extracts. For these extracts, optimized extraction and purification protocols were recently reported, which enable the efficient production of both hydrogenous and deuterated natural lipid mixtures. Deuterated lipids are of particular relevance for membrane characterization with techniques such as NMR, vibrational spectroscopies, and neutron scattering. In part III, we provide some future perspectives on the application of the currently available natural lipid extracts as well as on the development of protocols for the production of extracts from other cell types, e.g. mammalian cells and for isolating individual lipid molecules from such extracts. We also discuss methods to design genetically engineer microbial strains for enhancing the biosynthesis of target lipid molecules.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184474"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145298260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRAP mediated conformational changes of the human Sec61 channel","authors":"Nidhi Sorout,&nbsp;Volkhard Helms","doi":"10.1016/j.bbamem.2025.184488","DOIUrl":"10.1016/j.bbamem.2025.184488","url":null,"abstract":"<div><div>The integral membrane pore Sec61 catalyzes the translocation of many secretory precursor proteins into the endoplasmic reticulum, as well as the insertion of transmembrane proteins into the cell and organellar membranes. Precursor proteins that possess weak signal peptides frequently require presence of the accessory membrane protein TRAP. Structural biology has recently established that TRAP shares several contact sites with Sec61, though not by an extended binding interface. However, how TRAP mechanistically supports the translocation of precursor proteins is still partially unresolved. Here, atomistic molecular dynamics simulations revealed that TRAP binding keeps Sec61 in a partially opened state, with looser packing of its transmembrane helices. TRAP maintained a partially opened Sec61 lateral gate and pore ring, shifting the plug helix towards an open conformation. These observations corroborate the existing model of how TRAP may support translocation of client precursor proteins with weak signal peptides.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184488"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145614272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Interaction of N-terminal peptide analogues of the Na+,K+-ATPase with membranes” [BBA Biomembr. 1860 (6) (2018) 1282–1291]","authors":"Khoa Nguyen ,&nbsp;Alvaro Garcia ,&nbsp;Marc-Antoine Sani ,&nbsp;Vikas Dubey ,&nbsp;Daniel Clayton ,&nbsp;Giovanni Dal Poggetto ,&nbsp;Flemming Cornelius ,&nbsp;Richard J. Payne ,&nbsp;Frances Separovic ,&nbsp;Himanshu Khandelia ,&nbsp;Ronald J. Clarke","doi":"10.1016/j.bbamem.2025.184482","DOIUrl":"10.1016/j.bbamem.2025.184482","url":null,"abstract":"","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184482"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480895","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the impact of membrane fluidity in shaping lipid-based drug delivery systems development","authors":"Mariana Biscaia-Caleiras ,&nbsp;Ana Sofia Lourenço ,&nbsp;João Nuno Moreira ,&nbsp;Sérgio Simões","doi":"10.1016/j.bbamem.2025.184461","DOIUrl":"10.1016/j.bbamem.2025.184461","url":null,"abstract":"<div><div>Membrane fluidity is a fundamental property extensively studied in biological membranes and biophysical research, where it is critical to understanding membrane structure and function. However, its application in the development and manufacturing of lipid-based drug delivery systems, such as liposomes and lipid nanoparticles, remains underexplored. This mini-review shifts the focus toward the practical implications of membrane fluidity in pharmaceutical formulation and manufacturing. We highlight key factors influencing fluidity, such as temperature, lipid composition, and cholesterol content, and emphasize how understanding and controlling fluidity can serve as a critical quality attribute. The importance of these factors in modulating membrane dynamics is emphasized, revealing their potential to optimize liposomal formulations and manufacturing processes. Fluorescent probes such as DPH and Laurdan are also discussed for their ability to monitor fluidity in real-time, each presenting distinct advantages and limitations. Although its crucial role in lipid-based drug delivery systems, membrane fluidity remains a largely overlooked property. Deeper investigation is essential to fully understand its influence on membrane stability, therapeutic efficacy, and scalability. This mini-review advocates for a paradigm shift: recognizing membrane fluidity as a critical quality attribute that can be integrated into formulation development and industrial manufacturing frameworks to better predict and control product performance and process robustness.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184461"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune antibodies recognizing the stem region of SARS-CoV-2 spike protein: Molecular modeling and in vitro study of synthetic peptides presentation to the antibodies","authors":"Elena T. Aliper ,&nbsp;Ivan M. Ryzhov ,&nbsp;Polina S. Obukhova ,&nbsp;Alexander B. Tuzikov ,&nbsp;Oxana E. Galanina ,&nbsp;Marina M. Ziganshina ,&nbsp;Gennady T. Sukhikh ,&nbsp;Nikolay A. Krylov ,&nbsp;Stephen M. Henry ,&nbsp;Roman G. Efremov ,&nbsp;Nicolai V. Bovin","doi":"10.1016/j.bbamem.2025.184472","DOIUrl":"10.1016/j.bbamem.2025.184472","url":null,"abstract":"<div><div>Antibodies to peptide 1147 (amino acids 1147–61) of the SARS-CoV-2 S protein are highly diagnostic. Peptide 1147, although located in a region that is partly spatially hidden in the intact protein, is not subject to mutations, suggesting therapeutic potential. The aim of this study was to elucidate the architecture of this region and the way in which it is presented to antibodies. As a model system, this peptide carrying a single lipophilic tail and the same peptide carrying a lipophilic tail at both ends (pseudocyclic) were incorporated into a lipid membrane. Isolated anti-1147 antibodies interacted with it regardless of how the peptide was presented, be that freely exposed via the N-terminus, organized as a pseudocycle, or adsorbed on the surface. Molecular dynamics simulations showed that peptide 1147 is capable of closely approaching the membrane. Analysis of the surface properties of peptide 1147 in membrane-bound states and in particular functional conformations in the full-sized S protein reveals an interface for interaction with antibodies. Interestingly, the latter bears similarities to one published peptide-antibody complex. However, these antibodies, in spite of their high diagnostic significance, show no virus-neutralizing activity, indicating that peptide 1147 has no therapeutic value as a synthetic vaccine.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184472"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"α,ω-Hexadecanedioic acid induces proton-translocating decoupling at complex III via Q-cycle disruption: evidence from kinetic and structural analyses","authors":"Svetlana I. Pavlova ,&nbsp;Victor N. Samartsev ,&nbsp;Alexander V. Chulkov ,&nbsp;Ekaterina I. Khoroshavina ,&nbsp;Mikhail V. Dubinin","doi":"10.1016/j.bbamem.2025.184476","DOIUrl":"10.1016/j.bbamem.2025.184476","url":null,"abstract":"&lt;div&gt;&lt;div&gt;This study investigates the interaction between α,ω-hexadecanedioic acid (HDA (&lt;span&gt;&lt;math&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;/math&gt;&lt;/span&gt;)) and сomplex III (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;mi&gt;III&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;) electron transport chain in liver mitochondria, focusing on &lt;span&gt;&lt;math&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;msub&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;mi&gt;III&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; complex formation during succinate and glutamate/malate oxidation. A key emphasis is placed on the “idling” state of &lt;span&gt;&lt;math&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;msub&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;mi&gt;III&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;, where electron transfer occurs without proton translocation. The decoupling effect of HDA was quantified using three parameters: 1) &lt;span&gt;&lt;math&gt;&lt;msubsup&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mi&gt;ap&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;msubsup&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mo&gt;∗&lt;/mo&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt;: apparent dissociation constants of the &lt;span&gt;&lt;math&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;msub&gt;&lt;mi&gt;E&lt;/mi&gt;&lt;mi&gt;III&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; complex, calculated based on the total HDA concentration and the HDA quantity within the mitochondrial effective volume, respectively; 2) &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mi&gt;Dmax&lt;/mi&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;: the maximal mitochondrial respiration rate under saturating HDA concentrations (as [HDA] approaches infinity); 3) &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mn&gt;0.5&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;: the HDA concentration at which the decoupling effect (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mi&gt;D&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mn&gt;4&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;) equals half of its maximal value (&lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mi&gt;Dmax&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;−&lt;/mo&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mn&gt;4&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;), where &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mn&gt;4&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; represents the mitochondrial respiration rate in State 4. Methodologies for parameter determination were established through HDA concentration-dependent respiration profiles. Key findings reveal that &lt;span&gt;&lt;math&gt;&lt;msubsup&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mi&gt;ap&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt; remains substrate-independent but in contrast to &lt;span&gt;&lt;math&gt;&lt;msubsup&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mo&gt;∗&lt;/mo&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt; varies with mitochondrial protein concentration. In contrast, &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mn&gt;0.5&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; and &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mi&gt;Dmax&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;/&lt;/mo&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mn&gt;4&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt; were significantly higher during succinate oxidation compared to glutamate/malate. Classical protonophores 3,5-di(tret-butyl)-4-hydroxybenzylidenemalononitrile (SF6847) and 2,4-dinitrophenol (DNP), as well as chenodeoxycholic acid (CDCA) at low concentrations, increased &lt;span&gt;&lt;math&gt;&lt;msubsup&gt;&lt;mi&gt;K&lt;/mi&gt;&lt;mi&gt;d&lt;/mi&gt;&lt;mi&gt;ap&lt;/mi&gt;&lt;/msubsup&gt;&lt;/math&gt;&lt;/span&gt; without affecting &lt;span&gt;&lt;math&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mi&gt;Dmax&lt;/mi&gt;&lt;/msub&gt;&lt;mo&gt;/&lt;/mo&gt;&lt;msub&gt;&lt;mi&gt;J&lt;/mi&gt;&lt;mn&gt;4&lt;/mn&gt;&lt;/msub&gt;&lt;/math&gt;&lt;/span&gt;, suggesting reduced HDA efficacy. Molecular docking identified potential HDA binding sites on сomplex III. Based on these findings, we discuss a possible mechanism underlying the decoupling action (intrinsic uncoupli","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184476"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145312257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reassessing DMSO–lipid interactions: Improved AMBER force fields emphasize solvent rather than bilayer effects in cryoprotection","authors":"Ivan Klbik ,&nbsp;Milan Melicherčík ,&nbsp;Dušan Račko ,&nbsp;Igor Maťko ,&nbsp;Ján Lakota ,&nbsp;Ondrej Šauša","doi":"10.1016/j.bbamem.2025.184481","DOIUrl":"10.1016/j.bbamem.2025.184481","url":null,"abstract":"<div><div>The interaction of dimethyl sulfoxide (DMSO) with lipid membranes has been extensively studied using molecular dynamics (MD) simulations, yet discrepancies with experimental findings persist. Here, we re-evaluate the effects of low DMSO concentrations (1.5–10 vol%) on dimyristoyl phosphatidylcholine (DMPC) membranes using updated AMBER force fields (LIPID17, OPC, GAFF2) to assess its cryoprotective role. Simulations were performed in both fluid (330<em>K</em>) and gel (260 K) phases as well as under ice-forming conditions. Across three independent replicas, no statistically significant effects of DMSO were detected on membrane thickness, area per lipid, hydration, or acyl-chain order, indicating that low levels of DMSO do not alter bilayer structure. This represents an improvement over earlier force-field descriptions, which often exaggerated DMSO–lipid interactions, and provides results more consistent with experimental evidence. DMSO showed mild enrichment at the hydrophobic–hydrophilic interface, particularly near carbonyl and glycerol groups, but most molecules remained in the solvent. The strongest effects therefore emerged in the solvent phase: DMSO slowed ice crystal growth by about a factor of five, was excluded from the ice lattice, and accumulated at the ice–membrane boundary forming an ice-free layer. Surprisingly, even without DMSO, ice formation in contact with the bilayer did not cause structural disruption, suggesting that cryoinjury involves additional membrane components beyond lipids. DMSO also strongly inhibited the temperature-driven variation of water density in the amorphous state. These findings suggest that at low concentrations, DMSO's cryoprotective action arises mainly from modulation of water and ice behavior rather than direct bilayer perturbation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184481"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145480817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temperature, pressure and salt effects on bilayers of an acidic phospholipid, dipalmitoylphosphatidylglycerol","authors":"Masaki Goto ,&nbsp;Saeko Tanaka ,&nbsp;Nobutake Tamai ,&nbsp;Hitoshi Matsuki","doi":"10.1016/j.bbamem.2025.184462","DOIUrl":"10.1016/j.bbamem.2025.184462","url":null,"abstract":"<div><div>The effects of thermal pretreatments and a monovalent added salt (NaCl) on the thermotropic and barotropic bilayer phase behavior of an acidic phospholipid, dipalmitoylphosphatidylglycerol (DPPG), were investigated by differential scanning calorimetry, fluorometry and light transmittance measurements. At 1.0 mol kg⁻¹ NaCl concentration, lipid samples with static annealing treatments (i.e., cold storage) showed a transition from a metastable hydrated crystalline phase to the lamellar gel phase in addition to the pre- and the main transition. These transition temperatures increased with pressure and the interdigitated gel phase was induced under high pressure, which is similar to the bilayer phase behavior of dipalmitoylphosphatidylcholine. By contrast, lipid samples with dynamic annealing treatments (i.e., repeated freeze-thaw cycles) exhibited only a transition from the stable hydrated crystalline phase to the liquid crystalline phase accompanied by the morphological change in the bilayer aggregate. The transition temperature also increased with pressure and the phase behavior resembled that of dipalmitoylphosphatidylethanolamine. Regarding the salt effect, we found that the temperature–pressure phase diagrams of the non-annealed DPPG bilayer changed systematically with the salt concentration, demonstrating that the pressure-induced interdigitation is suppressed by the added salt. Thermodynamic quantities of the phase transitions increased with increasing salt concentration, suggesting that the DPPG bilayer was stabilized by the weakening of the electrostatic repulsion among the polar head groups due to the shielding effect. The concentration dependence of the minimum interdigitation pressure indicates the possibility that the interdigitation should occur even under atmospheric pressure in the absence of the salt.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184462"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228397","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}