{"title":"Effect of membrane tension on (−)-epigallocatechin gallate-induced burst of single giant unilamellar vesicles","authors":"Yukihiro Tamba , Naoya Sugita , Mika Terada , Masahito Yamazaki","doi":"10.1016/j.bbamem.2025.184427","DOIUrl":"10.1016/j.bbamem.2025.184427","url":null,"abstract":"<div><div>(−)-Epigallocatechin gallate (EGCg), a tea catechin, exhibits antimicrobial activity. EGCg induces burst of giant unilamellar vesicles (GUVs), resulting in leakage of their internal contents. Here, we examined the effect of membrane tension on the EGCg-induced burst of dioleoylphosphatidylcholine (DOPC)-GUVs. The observation of the EGCg-induced burst of GUVs without membrane tension indicated that first a micropore was formed in the membrane and then its radius rapidly increased with time within ~10 ms without a change in the GUV diameter, and then the GUV diameter decreased to a lipid membrane aggregate. Next, we examined the effect of membrane tension on the EGCg-induced fractional area change (<em>δ</em>) of GUVs and its burst. During the interaction of EGCg with a GUV with low tension (≤ 0.5 mN/m), the <em>δ</em> initially increased slightly and then decreased to negative values, concomitant with the appearance of invaginated structures such as dense particles and narrow tubes in the GUV membrane and lumen, resulting in pore formation and subsequent GUV burst. By contrast, at higher tension, <em>δ</em> increased with time. The fraction of burst GUV after 5 min of interaction, <em>P</em><sub>burst</sub> (5 min), decreased with increasing tension up to 3.0 mN/m, indicating that membrane tension suppressed the burst. The <em>P</em><sub>burst</sub> (5 min) increased with increasing the fraction of GUVs in which invaginated structures appeared within 5 min of interaction, suggesting that the formation of invaginated structures may cause the initial EGCg-induced pore formation. We have proposed a mechanism of the tension effect on the EGCg-induced pore formation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184427"},"PeriodicalIF":2.8,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172125","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}
Valeriya Trusova, Uliana Malovytsia, Kateryna Vus, Olga Zhytniakivska, Galyna Gorbenko
{"title":"Amyloid-liposome composites as hybrid platforms for doxorubicin delivery","authors":"Valeriya Trusova, Uliana Malovytsia, Kateryna Vus, Olga Zhytniakivska, Galyna Gorbenko","doi":"10.1016/j.bbamem.2025.184426","DOIUrl":"10.1016/j.bbamem.2025.184426","url":null,"abstract":"<div><div>The feasibility of engineering the sophisticated hybrid drug delivery platforms through the integration of phospholipid vesicles within a matrix of amyloid suspensions has been evaluated. Utilizing the equilibrium dialysis methodology and spectrofluorometric technique, the quantitative analysis of doxorubicin (DOX) encapsulation capacity of diverse phospholipid assemblies, amyloid suspensions, and their corresponding composite systems has been performed. Our findings revealed that the incorporation of negatively charged cardiolipin (CL) into phosphatidylcholine (PC) lipid vesicles significantly enhances DOX encapsulation and retention, while the addition of amyloid fibrils to charged liposomes has minimal impact on the drug binding. The neutral PC liposomes modified with insulin and lysozyme fibrillar suspensions exhibited improved doxorubicin encapsulation and retention compared to unmodified liposomes, thereby displaying a potential for reduced toxicity and prolonged drug action <em>in vivo</em>. Notably, amyloid fibrils alone were found to demonstrate the lower degree of DOX encapsulation and retention as compared to liposomes. Fluorimetric analysis suggests that the presence of insulin and lysozyme fibrils alters the microenvironment of DOX towards a more hydrophobic which is consistent with deeper bilayer penetration. Cumulative data from release kinetics and retention studies along with fluorescence measurements suggest that PC liposome-insulin fibril composites represent the most promising DOX nanocarriers, combining enhanced drug encapsulation, structural stability, and optimal drug location within the bilayer. The results obtained provide valuable insights into the design of protein-lipid nanomaterials for enhanced drug delivery, offering promising avenues for the development of more effective and targeted therapeutic strategies.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184426"},"PeriodicalIF":2.8,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144130922","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}
Evelyn A. Okorafor , Emma A. Gordon , Indra D. Sahu , Muhammad Zeeshan Shah , Dominik Konkolewicz , Gary A. Lorigan
{"title":"Influence of lipid saturation on the structural properties of styrene maleic acid lipid nanoparticles (SMALPs)","authors":"Evelyn A. Okorafor , Emma A. Gordon , Indra D. Sahu , Muhammad Zeeshan Shah , Dominik Konkolewicz , Gary A. Lorigan","doi":"10.1016/j.bbamem.2025.184424","DOIUrl":"10.1016/j.bbamem.2025.184424","url":null,"abstract":"<div><div>Membrane bilayers are complex three-dimensional structures whose molecular events in the deep dimensions of membrane lipids are crucial for understanding membrane function. This study investigates the interaction of coexisting membrane domains in terms of hydrophobicity, alkyl chain order, and fluidity using Styrene Maleic Acid (SMA) copolymers as membrane mimics. We employed continuous wave electron paramagnetic resonance spectroscopy (CW-EPR) to characterize the structural dynamic properties of membrane domains without separation. Lipid-spin probe vesicles were prepared using phospholipids with varying degrees of saturation (DOPC, POPC, DMPC, and DSPC) and doxyl spin-labeled phospholipids at different depths (5, 12, and 16-doxyl PC) as membrane probes. These vesicles were titrated with two SMA polymers of different hydrophobic tail lengths. Dynamic light scattering (DLS) confirmed the formation of Styrene Maleic Acid lipid nanoparticles (SMALPs). CW-EPR spectroscopy was used to characterize the dynamic properties of vesicles incorporated into the SMALP systems. Analysis of the CW-EPR spectral line shape data revealed that the hydrophobic tail of SMA, the degree of lipid saturation, and the length of phospholipids significantly affect membrane fluidity and alkyl chain ordering, as well as lipid interactions. Notably, samples containing DSPC, a fully saturated longer-chain phospholipid, and those containing SMA exhibited increased rigidity of motion, reduced fluidity, and improved ordering of the alkyl chain in the membrane. This study provides crucial insights into the molecular dynamics of membrane bilayers and the impact of SMA copolymers on membrane properties, contributing to our understanding of fundamental membrane functions such as lateral movement of proteins and lipids.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184424"},"PeriodicalIF":2.8,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141407","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":"Evaluation of aquaporin Z water permeability in bilayers using droplet interface systems with internal-pressure–defined membrane tension","authors":"Misuzu Ueki , Takahisa Maki , Masayuki Iwamoto","doi":"10.1016/j.bbamem.2025.184425","DOIUrl":"10.1016/j.bbamem.2025.184425","url":null,"abstract":"<div><div>Cell membranes regulate water flow to maintain homeostasis, cell volume, and osmotic balance. Aquaporins (AQPs) enable selective water transport, making precise permeability measurements essential for understanding their function. The current methods have limitations, including high resource demands and poor control over membrane properties like bilayer tension. In this study, the droplet interface bilayer (DIB) system was used to measure aquaporin water channel activity. Unlike conventional water permeability assays, this method uniquely quantifies lipid bilayer tension by determining droplet internal pressure. This pressure-determined DIB (PDIB) method was used to investigate the water permeability of a lipid bilayer reconstituted with <em>Escherichia coli</em> aquaporin Z (AqpZ). Water permeability increased in an AqpZ concentration-dependent manner at bilayer tensions of 2.2–3.0 mN/m and was inhibited by mercury (IC<sub>50</sub>, 340 μM). Fluorescence microscopy was performed to visualize and quantify AqpZ molecules, thereby allowing us to derive an approximate estimate of the unitary water permeability. Although this study established the PDIB method and demonstrated its applicability to AqpZ, this technique may also facilitate future investigations on the effects of lipid bilayer tension on aquaporin function and the fundamental mechanisms of water transport across biological membranes.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184425"},"PeriodicalIF":2.8,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144115070","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":"Interactions of hinokitiol with fungal membrane lipids in model systems","authors":"Beata Wyżga , Magdalena Skóra , Karolina Olechowska , Katarzyna Hąc-Wydro","doi":"10.1016/j.bbamem.2025.184423","DOIUrl":"10.1016/j.bbamem.2025.184423","url":null,"abstract":"<div><div>Hinokitiol (β-thujaplicin) is a naturally occurring substance of antimicrobial properties, which can be used e.g. as a cosmetic preservative. In this work the influence of hinokitiol on the monolayers and bilayers formed from fungal membrane lipids (1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphoethanolamine – POPE; 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine – POPC and ergosterol) was investigated. These studies aimed to investigate the effect of hinokitiol on fungal membranes, being indicated as a target for this compound. In this context, the affinity of hinokitiol for ergosterol-containing membranes was of particular interest. The in vitro antifungal activity of hinokitiol was also determined. The results showed that hinokitiol is active against the <em>Candida</em> species tested and exhibits stronger antifungal than antibacterial activity. Moreover, hinokitiol alters the properties of model membranes and the observed effects correlated with ergosterol content in the system. Namely, the higher the ergosterol content, the greater the fluidizing and destabilising effect of hinokitiol and its removal from the model. Moreover, hinokitiol is not able to penetrate into ergosterol membranes; instead, causes strong destabilization of the film and dragging the monolayer material into the subphase. Thus, hinokitiol changes properties of model membrane by the exclusion of the molecules from the interface. The results evidenced differences in the interactions of hinokitiol with ergosterol vs phospholipids, and the interactions of hinokitiol with the membrane depend on the presence and levels of ergosterol. Thus, ergosterol can be a molecular target for this compound. Moreover, the presence of ergosterol in fungal membranes and its lack in bacteria membranes may explain stronger antifungal vs antibacterial effect of hinokitiol.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184423"},"PeriodicalIF":2.8,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143916398","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":"Effect of glucosylation for the vertical movement of cholesterol in bilayer membranes","authors":"Shinya Hanashima , Takafumi Asahina , Raymond Malabed , Katsuaki Sasaki , Michio Murata","doi":"10.1016/j.bbamem.2025.184422","DOIUrl":"10.1016/j.bbamem.2025.184422","url":null,"abstract":"<div><div>Cholesterol (Chol) in mammalian cell membranes facilitates the assembly of dynamic membrane domains that are involved in vital biological processes through lateral and transbilayer movements in the membranes. In the cell membranes, Chol undergoes glucose transglycosylation to produce cholesteryl-β-<span>d</span>-glucoside (ChoGlc). ChoGlc is involved in neurodegenerative diseases and accumulates in lysosomal storage disorders. However, the effects of glucosylation on membrane properties of Chol remain unclear. We investigated the membrane interaction of ChoGlc and its subsequent translocation between leaflets using fluorescent probes, such as 4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH) and the newly synthesized 7-nitro-2,1,3-benzoxadiazole-labeled ChoGlc (NBD-ChoGlc) in dioleoylphosphatidylcholine (DOPC) membranes. The fluorescence of TMA-DPH, which selectively reported the order of the outer leaflet of the bilayer, indicated that ChoGlc added to the external solution, was mostly incorporated into the membranes and increased the DOPC membrane ordering. Furthermore, the anisotropy values reached a level similar to that of the ChoGlc-preloaded symmetric vesicle within approximately 5 min owing to the rapid distribution of ChoGlc in both leaflets. This was further confirmed by the selective fluorescence quenching of NBD-ChoGlc in the outer leaflet through irreversible quenching by dithionite. The similarity of the fluorescence decay curves of NBD-ChoGlc and NBD-Chol indicated that the glucosylation had little impact on the flip-flops of Chol in the DOPC bilayers. Our data demonstrates that some of the important membrane properties of Chol, such as fast flip-flop between leaflets and increased membrane order, were mostly maintained in ChoGlc despite hydrophilic glucose modification.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 5","pages":"Article 184422"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143918419","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}
Martin Luther John , Sivaramakrishna Akella , Ravi Kanth Kamlekar
{"title":"Elucidating the interactions of endocannabinoid-like neurotransmitters, N-acyltaurines and bovine serum albumin: Spectroscopic and computational approaches","authors":"Martin Luther John , Sivaramakrishna Akella , Ravi Kanth Kamlekar","doi":"10.1016/j.bbamem.2025.184421","DOIUrl":"10.1016/j.bbamem.2025.184421","url":null,"abstract":"<div><div><em>N</em>-Acyltaurines (NATs) are endogenous neurotransmitters, structurally similar to endocannabinoids, and have anti-inflammatory and anti-proliferative effects. In response to NATs, TRP channels, TRPV1, TRPV4 and the peptide hormone, GLP-1 are activated. Serum albumin proteins act as transporters for a variety of substances in blood plasma (i.e., hormones, fatty acids, bilirubin, ions, and medications). Due to the structural closeness of Bovine Serum Albumin (BSA) and Human Serum Albumin (HSA), a study into NAT-BSA interactions is crucial. To study interactions of NATs (<em>n</em> = 10–18) with BSA, spectroscopic and computational techniques were used. From the steady-state fluorescence measurements, observed binding constants are in the range of 1.57 × 10<sup>5</sup> M<sup>−1</sup> to 2.85 × 10<sup>5</sup> M<sup>−1</sup>. Due to the binding of NATs, the fluorescence of BSA is quenched (∼24.77 %). The negative enthalpy and entropy change and Gibbs free energy values, obtained from van't Hoff plot indicate that the interactions between NATs and BSA are spontaneous and primarily driven by hydrogen bonding. Competitive site-binding assays with warfarin and ibuprofen show that NATs bind to both the drug-binding sites in BSA concurrently. The CD spectroscopic and FT-IR analysis indicates relatively marginal changes in the secondary structure of BSA. Molecular docking analyses are done to identify binding locations and molecular-level interactions. The negative free energy values indicate that NATs have a positive binding relationship with BSA. These findings are congruent with the findings of site-binding studies, which reveal that NATs have a higher proclivity for interacting with sites I and II at the same time.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184421"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143844050","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}
Angelo Santoro , Michela Buonocore , Anna Maria D'Ursi
{"title":"Effect of osmolytes on the conformational stability of Aβ(25–35): A circular dichroism analysis","authors":"Angelo Santoro , Michela Buonocore , Anna Maria D'Ursi","doi":"10.1016/j.bbamem.2025.184420","DOIUrl":"10.1016/j.bbamem.2025.184420","url":null,"abstract":"<div><div>Alzheimer's (AD) is a neurodegenerative disease characterized by the onset and progression of mental decline. AD aetiopathogenesis is still questioned; however, according to one of the most accredited hypotheses, the accumulation of amyloid plaques formed by aggregated Aβ peptides is the primary cause of neuronal function loss. Accordingly, hundreds of molecules have been screened for their possible action to prevent or destroy amyloid aggregates. Following this track, osmolytes, naturally occurring small molecules produced by several organisms in response to external stressors, were recently evaluated as modulators of Aβ aggregation. In this study, we examined the conformational stability of Aβ(25–35) when exposed to the osmolytes acetylcholine (ACh), succinylcholine (SCh), and betaine (Bet). Aβ(25–35) is the shortest fragment known for replicating the aggregation process seen in Aβ peptides. By collecting circular dichroism (CD) spectra in water and different membrane-mimicking systems, we investigated the potential of the mentioned osmolytes to stabilize the soluble conformations of Aβ(25–35) and preserve them from denaturing conditions. Our data suggest that Bet is a promising small molecule that can safeguard the soluble form of Aβ peptide and is effective in counteracting environmental conditions by favoring the amyloid aggregation associated with pathology progression.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184420"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787660","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yago Radziunas-Salinas , Vicente Domínguez-Arca , Alberto Pardo , Adriana Cambón , Pablo Taboada , Gerardo Prieto
{"title":"Long-chain cationic gemini surfactants as drug retention adjuvant on liposomes. A methodological approach with atorvastatin","authors":"Yago Radziunas-Salinas , Vicente Domínguez-Arca , Alberto Pardo , Adriana Cambón , Pablo Taboada , Gerardo Prieto","doi":"10.1016/j.bbamem.2025.184419","DOIUrl":"10.1016/j.bbamem.2025.184419","url":null,"abstract":"<div><div>This study delves into the development and characterization of dipalmitoyl phosphatidylcholine (DPPC) liposomes incorporated with gemini surfactant (tetradecamethylene-1,14 bis(dimethyl tetradecyl ammonium bromide); 14-14-14) and atorvastatin, aimed at enhancing drug delivery efficiency for cardiovascular diseases. The integration of gemini surfactants into liposomes is investigated for its potential to improve atorvastatin encapsulation and retention, addressing the drug's poor water solubility and the limitations of conventional liposomal systems. Through a combination of dynamic light scattering (DLS), differential scanning calorimetry (DSC), and molecular dynamics (MD) simulations, the study reveals that the presence of gemini surfactants significantly reduces liposome size and polydispersity, indicative of a more uniform and potentially unilamellar structure. DSC analysis highlights a decrease in transition temperatures and an alteration in transition symmetry, suggesting enhanced stability and a favourable drug release profile at physiological temperatures. MD simulations provide insight into the internalization mechanism of gemini surfactants and atorvastatin within the liposomal bilayer, demonstrating their mutual incorporation facilitated by polar interactions. Spectrophotometry-based retention studies further confirmed that liposomes containing gemini surfactants exhibit superior atorvastatin retention capabilities, nearly doubling the encapsulation efficiency compared to conventional liposomes. This research highlights the promising role of gemini surfactant-incorporated liposomes as an efficient drug delivery platform for cardiovascular therapeutics, offering insights into the molecular interactions and structural dynamics underlying their enhanced performance.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1867 4","pages":"Article 184419"},"PeriodicalIF":2.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787602","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}