Biochimica et biophysica acta. Biomembranes最新文献

{"title":"Sequence-dependent transferability of the LRLLR membrane translocation motif: A computational study of smacN and NR2B9c peptides.","authors":"D Muñoz-Gacitúa, Jenny Blamey","doi":"10.1016/j.bbamem.2026.184572","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184572","url":null,"abstract":"<p><p>The LRLLR cell-penetrating motif can be transferred to confer membrane translocation activity, but only to compatible recipient peptides. Using umbrella sampling molecular dynamics simulations, we show that C-terminal LRLLR addition to the pro-apoptotic smacN peptide eliminates its translocation barrier, transforming a + 65 kJ/mol barrier into a - 50 kJ/mol energy well. In contrast, N-terminal LRLLR addition to the neuroprotective NR2B9c peptide increases the barrier from +85 to +100 kJ/mol. The LRLLR pentapeptide, identified through systematic screening as essential for spontaneous translocation, represents a minimal penetrating element whose transferability was unknown. We appended this motif to both peptides and calculated potential of mean force profiles across a POPC/POPG bilayer. Analysis of hydrogen bonding patterns, secondary structure, and conformational dynamics reveals the structural basis for these divergent outcomes. Successful transfer to smacN reflects favorable charge complementarity: the hydrophobic, neutral AVPI tetrapeptide provides an ideal platform for the charged, amphipathic LRLLR motif, enabling simultaneous interaction with both membrane leaflets. Transfer failure with NR2B9c stems from its positive charge and conformational rigidity imposed by intramolecular hydrogen bonding, preventing optimal membrane insertion. These findings establish that CPP motif transfer requires compatibility in charge distribution, hydrophobicity, and conformational flexibility, and demonstrate the value of computational screening to identify compatible motif-cargo pairings prior to experimental investment.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184572"},"PeriodicalIF":2.4,"publicationDate":"2026-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148896609","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":"Mass photometry and its expanding role in membrane protein research: The Torpedo marmorata nicotinic acetylcholine receptor as case study.","authors":"Sarah Delaux, Korantin le Mouël, Nathalie Barilone, Jerome Castel, Marie Prevost, Oscar Hernandez-Alba, Pierre-Jean Corringer, Manuela Zoonens, Sarah Cianférani","doi":"10.1016/j.bbamem.2026.184574","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184574","url":null,"abstract":"<p><p>Integral membrane proteins (IMPs) are challenging, yet highly relevant targets for structural biology. Selection of the appropriate membrane mimic environment necessitates extensive optimization using a combination of biochemical and biophysical techniques. We report here on the expanding role of mass photometry (MP) as an in-solution technique to enable single-particle analysis of IMPs. To showcase MP versatility, we present here a selection of examples of MP applications for IMP analysis, using nicotinic acetylcholine receptor (nAChR) extracted from Torpedo marmorata as case study, together with additional literature examples. We further illustrate how MP supports the screening of purification conditions, and the quality control of samples prior to cryo-electron microscopy grid preparation or native mass spectrometry. The benefits of MP for IMP characterization are illustrated through its ability to quantify single-molecule populations, study membrane biomolecular assemblies, and characterize membrane-associated phenomena from very low amounts of starting material. MP therefore stands out as a unique biophysical tool that combines rapid analysis with broad adaptability to most solubilizing environments, enabling simultaneous relative quantification of all detected species in a highly user-friendly manner.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184574"},"PeriodicalIF":2.4,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886114","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":"Characterization of glycosaminoglycan interactions with the chemokine CCL20 (MIP3α) and its carboxyterminal antimicrobial and antibiofilm peptide.","authors":"Gopal Ramamourthy, Hiroaki Ishida, Hans J Vogel","doi":"10.1016/j.bbamem.2026.184569","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184569","url":null,"abstract":"<p><p>The chemokine CCL20/MIP3α plays an important role in the migration of dendritic cells and several lymphocytes. This 70-residue protein is also implicated in various diseases, such as rheumatoid arthritis, psoriasis, sepsis and numerous forms of cancer. In addition, as the most basic human chemokine, CCL20 also displays direct antimicrobial and antibiofilm activities. The binding and oligomerization of chemokines to cell surface glycosaminoglycans (GAG) can play an important role during receptor activation; therefore we have studied the interactions of CCL20 with fondaparinux. This anticoagulant drug is a uniform sulfated linear pentasaccharide that structurally closely resembles the heterogenous low molecular weight heparins that have often been used to study GAG-protein binding in solution. Using multidimensional multinuclear NMR spectroscopy, we could map out the distinct GAG/fondaparinux binding sites on the monomeric (pH 5.5) and dimeric (pH 7.5) forms of the CCL20 protein surface. In the second part of this study, we showed that CCL20-(51-70), the recombinant 20-residue carboxyterminal helical peptide of CCL20, interacted weakly with fondaparinux. We also surveyed several host-defence properties of this peptide. In comparison to several other well-characterized peptides, CCL20-(51-70) displayed potent antibiofilm and antimicrobial activities against a pathogenic Gram-positive Staphylococcus aureus MRSA strain. It also displayed somewhat lower activities against the Gram-negative Pseudomonas aeruginosa PAO1 strain. These results highlight the potential of CCL20-(51-70) as a potent host-defence peptide, that could play a role in eradicating bacterial biofilms, particularly for Gram-positive pathogenic bacteria.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184569"},"PeriodicalIF":2.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879111","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":"Calix[4]arene C-1220 - Modulator of calcium homeostasis and contractile activity in smooth muscle cells.","authors":"Tetyana O Veklich, Olga V Tsymbalyuk, Oleksandr V Maliuk, Lidiya G Babich, Sergiy G Shlykov, Sergiy O Cherenok, Sergiy O Karakhim, Anna I Selikhova, Vitaly I Kalchenko, Sergiy O Kosterin","doi":"10.1016/j.bbamem.2026.184573","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184573","url":null,"abstract":"<p><p>Regulation of Na⁺,K⁺-ATPase activity plays a critical role in maintaining ionic homeostasis and Ca²⁺-dependent contractility in smooth muscle, yet the contribution of selective sodium pump modulators to myometrial function remains insufficiently understood. In this study, we investigated the effects of calix[4]arene C-1220 (25,27-dipropoxycalix[4]arene-bis-N-tolylsulfonylaminomethylphosphonic acid) and its structural analogue C-99 on ATP-hydrolyzing activities, intracellular Ca²⁺ dynamics, mitochondrial function, and contractile behavior of uterine smooth muscle. Enzymatic assays showed that C-1220 is a highly potent and selective inhibitor of Na⁺,K⁺-ATPase (IC₅₀ = 48 ± 2 nM) without influencing other ATPases in the plasma membrane. Confocal imaging demonstrated that C-1220 elevates cytosolic Ca²⁺ in myocytes, whereas flow cytometry and Ca²⁺-accumulation assays indicated that mitochondrial membrane polarization and matrix Ca²⁺ levels remain unaffected. Tensometric measurements revealed that both C-1220 and C-99 enhance spontaneous contractions and force-, velocity-, and impulse-related mechanokinetic parameters; however, normalization of velocity parameters suggests that these changes do not reflect direct modulation of Ca²⁺-transporting systems. Comparative analysis supports the conclusion that inhibition of Na⁺,K⁺-ATPase and consequent disturbance of Na⁺/Ca²⁺ exchange underlie the contractile activation induced by both compounds. These findings provide new insights into membrane mechanisms governing electro- and pharmacomechanical coupling in uterine smooth muscle and highlight C-1220 as a useful molecular tool for probing Na⁺,K⁺-ATPase-dependent Ca²⁺ regulation.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184573"},"PeriodicalIF":2.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148872771","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 \"Topological mapping establishes signal peptide-independent cytoplasmic membrane insertion of bacterial MATE family efflux protein EmmdR\" [BBA - Biomembranes, 1868 (2026), 184566].","authors":"Hitkarsh Kushwaha, Jiban Mishra, Harapriya Mohapatra","doi":"10.1016/j.bbamem.2026.184571","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184571","url":null,"abstract":"","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184571"},"PeriodicalIF":2.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148849679","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":"Composition-tunable H-PC/LPC discoidal lipid assemblies: molecular packing, nanoscale organization, and permeation behavior.","authors":"Toshihiro Mori, Nanami Kiriyama, Mayuko Miyanishi, Katsunori Yoshida, Yoshihiro Tokudome","doi":"10.1016/j.bbamem.2026.184570","DOIUrl":"10.1016/j.bbamem.2026.184570","url":null,"abstract":"<p><p>Discoidal membrane-like lipid assemblies provide a useful framework for linking lipid composition to nanoscale organization and interfacial transport, but practical solvent-avoiding routes from formulation-compatible phospholipids remain limited. Here, hydrogenated phosphatidylcholine (H-PC)/lysophosphatidylcholine (LPC) dispersions were prepared in the presence of 1,3-butylene glycol (BG) by a simple heating-stirring procedure that avoids organic solvents used in thin-film hydration. Varying the H-PC/LPC ratio revealed a composition window in which transparent nanoscale dispersions with apparent hydrodynamic diameters of 10-20 nm were obtained. TEM and ³¹P NMR analyses most clearly supported discoidal assemblies with bicelle-like features at intermediate LPC fractions, whereas lower LPC fractions yielded lamellar/vesicular aggregates and higher LPC fractions showed smaller, more isotropic aggregate states. DSC showed a decrease in the main endothermic transition temperature with increasing LPC fraction, consistent with composition-dependent thermotropic phase behavior and altered packing compatibility between H-PC-rich ordered domains and LPC-rich components. In Franz diffusion experiments using caffeine as a hydrophilic probe, H-PC/LPC dispersions showed higher permeation across Strat-M® membranes than a BG-matched lipid-free control. Compared with LPC-only formulations, the mixed H-PC/LPC series showed a clearer composition-dependent permeation profile, indicating that permeation behavior is associated with the nanoscale state of the mixed lipid dispersion rather than LPC content alone. A representative discoidal-assembly composition gave a numerically higher cumulative permeated amount across excised human skin. These results identify a practical route to composition-tunable H-PC/LPC lipid assemblies with discoidal, bicelle-like features and show that molecular packing and aggregate organization are linked to permeation behavior at biological interfaces.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184570"},"PeriodicalIF":2.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148824594","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":"Hydrophilic lipophilic balance: A lighthouse parameter for designing efficient detergents in membrane protein applications?","authors":"Marine Soulié, Grégory Durand","doi":"10.1016/j.bbamem.2026.184564","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184564","url":null,"abstract":"<p><p>Since the 1970s, the hydrophilic lipophilic balance (HLB) has been widely recognized as a key parameter for evaluating the effectiveness of detergents across various fields, including membrane protein (MP) research. Detergents play a crucial role in the structural and functional characterization of membrane proteins: they disrupt the lipid bilayer, provide a stabilizing environment that maintains both protein solubility and native conformation, and facilitate subsequent crystallization. In this review, we trace the integration of the HLB concept into detergent development for membrane protein studies over the past 55 years. We revisit foundational work demonstrating that effective detergents span a wide range of HLB values. We highlight recent advances involving diverse detergent classes, including hydrogenated, fluorinated, cyclic, and linear molecules, to illustrate the continuing relevance of the HLB as a guiding parameter in detergent design. HLB values of well-established and widely used detergents are put into perspective alongside those of recently synthesized compounds to offer valuable insights into their performance in membrane protein studies and guide the rational design of next-generation detergents. Finally, we discuss how chemists and biochemists strategically apply the HLB parameter to optimize detergent design for membrane protein research.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184564"},"PeriodicalIF":2.4,"publicationDate":"2026-07-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148598495","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":"Collective lipid dynamics in biomembranes.","authors":"Michael F Brown","doi":"10.1016/j.bbamem.2026.184553","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184553","url":null,"abstract":"<p><p>Cellular lipids are wonders of biomolecular self-organization whose structure and dynamics are intimately connected with their functionality. Here we review the development and use of NMR spectroscopy in the study of lipid membranes. For liquid-crystalline bilayers, the structure is described by orientational order parameters, while the dynamics entail fluctuations about the mean geometry. Addressing the information gap between molecular structure, dynamics, and function involves magnetic resonance spectroscopy combined with X-ray and neutron scattering approaches. Cholesterol gives a crucial test in liquid-ordered (l_o) membranes, where the bending rigidity oppositely affects solid-state NMR observables-the order parameters increase yet the relaxation rates decrease. By contrast, nonionic surfactants in the liquid-disordered (l_d) state soften the bilayer and decrease the order parameters, thereby enhancing the spin relaxation. This enigma is explained by a model-free power-law that combines the mean-squared amplitudes and fluctuation rates. Collective modes appear on the mesoscale of the bilayer thickness and less, indicating how membrane elasticity emerges from atomistic-level interactions that drive the response to external forces. The unified power-law scaling shows how the bilayer fluidity corresponds to a hydrocarbon liquid of similar chain length. Magnetic resonance spectroscopy thus yields insights into properties that underlie bilayer phase transitions, curvature, and protein-lipid interactions.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184553"},"PeriodicalIF":2.4,"publicationDate":"2026-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148275889","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":"Blood coagulation protein binds to Ca2+-induced phosphatidylserine nanodomains as revealed by atomic force microscopy","authors":"Jie Cheng ,&nbsp;Junhong Lü ,&nbsp;Xueling Li","doi":"10.1016/j.bbamem.2026.184500","DOIUrl":"10.1016/j.bbamem.2026.184500","url":null,"abstract":"<div><div>The interaction between coagulation factor VIII (FVIII) and phospholipid membranes is a critical aspect of the blood clotting process. While it is known that FVIII binds to negatively charged phospholipids, the role of calcium ions (Ca²⁺) in this process remains an area of ongoing research. This study investigated the dynamic effects of Ca²⁺ on FVIII binding to phospholipid membranes, in particular how Ca²⁺-induced nanodomain formation affects this interaction. Using in situ atomic force microscopy (AFM) imaging, we observed the morphological and structural changes of supported lipid bilayers (DPPC/DOPS and DOPC/DPPS systems) in response to Ca²⁺. The results showed that Ca²⁺ not only alters the membrane lipid structure, but also promotes the formation of nanodomain in the phosphatidylserine (PS)-enriched regions. In the presence of Ca²⁺, FVIII bound preferentially to PS nanodomains with height differences of about 0.8 nm compared to adjacent membrane regions, and the binding process was further facilitated by Ca²⁺-induced reorganization of the lipid phases over time scales of 40–230 min. These findings provided new insights into the molecular mechanisms governing the interaction of FVIII with phospholipid membranes and underlined the crucial role of Ca²⁺ in supporting the functional activity of coagulation protein.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184500"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146002972","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":"Acylation of the RTX toxin MbxA stimulates host membrane disruption through a specific interaction with cholesterol","authors":"Feby Mariam Chacko ,&nbsp;Sarah Michelle Ganz ,&nbsp;Anne Pfitzer-Bilsing ,&nbsp;Sebastian Hänsch ,&nbsp;Philipp Westhoff ,&nbsp;Stefanie Weidtkamp-Peters ,&nbsp;Sander H.J. Smits ,&nbsp;Marten Exterkate ,&nbsp;Lutz Schmitt","doi":"10.1016/j.bbamem.2025.184487","DOIUrl":"10.1016/j.bbamem.2025.184487","url":null,"abstract":"<div><div>RTX toxins (Repeat in ToXins) are pore-forming toxins secreted by gram-negative bacteria. They are known for their ability to disrupt host cell membranes, among which various human cells. The acylation of specific lysine residues in these toxins is crucial for their hemolytic activity, but the precise mechanisms underlying this enhancement remain unclear. By comparing the lytic activities of acylated MbxA and its non-acylated form, we explored the role of acylation in the pore-forming behavior of this RTX toxin. Our findings demonstrate that acylation specific interactions of MbxA with cholesterol promote membrane disruption, both <em>in vitro</em> and in living cells. More specifically, acylation is not necessary for initial membrane binding, but markedly enhances pore formation. Overall, our results provide detailed insights into the molecular determinants that regulate MbxA toxin activity. We highlight a complex interplay between lipid composition (sterols), acylation, and membrane disruption, thereby advancing our general understanding of RTX toxin pathogenesis.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184487"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145628387","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}