Pub Date : 2026-03-19DOI: 10.1016/j.bbamem.2026.184523
Jesus Ayala-Sanmartin, Antonin Lamazière
The role of cholesterol in membrane lipid organization and ordering has been evidenced over the past twenty years. The participation of cholesterol precursors and other cholesterol derivatives in the modulation of cell membrane physicochemical properties is less well documented. Herein, an investigation into the effects of cholesterol, two cholesterol precursors (desmosterol and lanosterol) and two hydroxylated metabolites (24S-hydroxycholesterol and 25-hydroxycholesterol) on membrane dynamics was performed. The differences between sphingomyelin- and ceramide-containing membranes were investigated using membrane models that mimic the plasma membrane. Two fluorescent probes were used to study the ordering power and molecular mobility: Laurdan, a sensor of membrane polarity and lipid order near the lipid head groups, and cholesterol-pyrene, a sensor of order near the center of the membrane. The results showed that the double bond in the sterol tail of desmosterol modified the molecular dynamics near the bilayer center resulting in less order in ceramide membranes than in sphingomyelin membranes. The methyl groups on the sterol rings of lanosterol induced increased polarity and decreased order near the lipid head groups, and the hydroxyl groups in the 24 and 25 carbons of the sterol tail changed membrane properties across the membrane axis in a complex manner. These results suggest that the differences in the intra- and intermolecular hydrogen bonding capacities of ceramide and sphingomyelin with specific sterols are in part responsible for specific physicochemical modifications of membranes properties.
{"title":"Differential lipid dynamics regulation by sterols in ceramide and sphingomyelin containing membranes.","authors":"Jesus Ayala-Sanmartin, Antonin Lamazière","doi":"10.1016/j.bbamem.2026.184523","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184523","url":null,"abstract":"<p><p>The role of cholesterol in membrane lipid organization and ordering has been evidenced over the past twenty years. The participation of cholesterol precursors and other cholesterol derivatives in the modulation of cell membrane physicochemical properties is less well documented. Herein, an investigation into the effects of cholesterol, two cholesterol precursors (desmosterol and lanosterol) and two hydroxylated metabolites (24S-hydroxycholesterol and 25-hydroxycholesterol) on membrane dynamics was performed. The differences between sphingomyelin- and ceramide-containing membranes were investigated using membrane models that mimic the plasma membrane. Two fluorescent probes were used to study the ordering power and molecular mobility: Laurdan, a sensor of membrane polarity and lipid order near the lipid head groups, and cholesterol-pyrene, a sensor of order near the center of the membrane. The results showed that the double bond in the sterol tail of desmosterol modified the molecular dynamics near the bilayer center resulting in less order in ceramide membranes than in sphingomyelin membranes. The methyl groups on the sterol rings of lanosterol induced increased polarity and decreased order near the lipid head groups, and the hydroxyl groups in the 24 and 25 carbons of the sterol tail changed membrane properties across the membrane axis in a complex manner. These results suggest that the differences in the intra- and intermolecular hydrogen bonding capacities of ceramide and sphingomyelin with specific sterols are in part responsible for specific physicochemical modifications of membranes properties.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184523"},"PeriodicalIF":2.5,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147493569","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}
Pub Date : 2026-03-18DOI: 10.1016/j.bbamem.2026.184522
M Eranjalee Ranaweera, Rebecca J Jernigan, Krisha S Boradia, Kelli L Trimble, Vasiliy A Loskutov, Jose M Martin-Garcia, Lynn Goss Schrag, Felicia M Craciunescu, Timothy L Karr, Krishna Parsawar, Ning Zhang, Debra T Hansen, Petra Fromme
Francisella tularensis, the causative agent of tularemia, relies on the CapBCA membrane protein complex for intracellular survival and virulence, yet none of its components have been structurally characterized. Here, we report successful recombinant expression, membrane targeting, and purification of the CapB and CapC proteins from F. tularensis SCHU S4 using an N-terminal PelB-MBP fusion strategy. Both proteins were efficiently delivered to the inner membrane of Escherichia coli, solubilized in β-DDM detergent, and purified in monodisperse form with yields of approximately 5 mg per 4 L culture. Size exclusion chromatography, Blue Native PAGE, dynamic light scattering, and negative-stain electron microscopy consistently indicated that the maltose-binding protein tagged CapB and CapC each formed detergent-stabilized oligomers. Circular dichroism spectroscopy showed predominantly α-helical secondary structure content for both proteins and revealed differential sensitivity to ionic strength. Structural predictions using AlphaFold 3 and membrane-interaction modeling support the presence of one transmembrane helix for CapB and five for CapC, consistent with their hydropathy profiles. These results provide the first biochemical and structural characterization of CapB and CapC, enabling future high-resolution studies of the CapBCA complex and advancing efforts to understand its role in F. tularensis virulence and potential therapeutic targeting.
{"title":"Purification and structural characterization of the tularemia membrane protein virulence factors CapB and CapC.","authors":"M Eranjalee Ranaweera, Rebecca J Jernigan, Krisha S Boradia, Kelli L Trimble, Vasiliy A Loskutov, Jose M Martin-Garcia, Lynn Goss Schrag, Felicia M Craciunescu, Timothy L Karr, Krishna Parsawar, Ning Zhang, Debra T Hansen, Petra Fromme","doi":"10.1016/j.bbamem.2026.184522","DOIUrl":"https://doi.org/10.1016/j.bbamem.2026.184522","url":null,"abstract":"<p><p>Francisella tularensis, the causative agent of tularemia, relies on the CapBCA membrane protein complex for intracellular survival and virulence, yet none of its components have been structurally characterized. Here, we report successful recombinant expression, membrane targeting, and purification of the CapB and CapC proteins from F. tularensis SCHU S4 using an N-terminal PelB-MBP fusion strategy. Both proteins were efficiently delivered to the inner membrane of Escherichia coli, solubilized in β-DDM detergent, and purified in monodisperse form with yields of approximately 5 mg per 4 L culture. Size exclusion chromatography, Blue Native PAGE, dynamic light scattering, and negative-stain electron microscopy consistently indicated that the maltose-binding protein tagged CapB and CapC each formed detergent-stabilized oligomers. Circular dichroism spectroscopy showed predominantly α-helical secondary structure content for both proteins and revealed differential sensitivity to ionic strength. Structural predictions using AlphaFold 3 and membrane-interaction modeling support the presence of one transmembrane helix for CapB and five for CapC, consistent with their hydropathy profiles. These results provide the first biochemical and structural characterization of CapB and CapC, enabling future high-resolution studies of the CapBCA complex and advancing efforts to understand its role in F. tularensis virulence and potential therapeutic targeting.</p>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":" ","pages":"184522"},"PeriodicalIF":2.5,"publicationDate":"2026-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490419","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}
Pub Date : 2026-01-01Epub Date: 2025-10-12DOI: 10.1016/j.bbamem.2025.184473
Mikhail V. Dubinin , Anna I. Ilzorkina , Anastasia D. Igoshkina , Natalia V. Mikina , Rezeda R. Khalitova , Nikita V. Penkov , Natalia V. Belosludtseva , Anna Y. Spivak , Konstantin N. Belosludtsev
This study shows the effects of phenolic acids (gallic, coumaric, caffeic, and ferulic) and their triphenylphosphonium (TPP+) derivatives on the state of liposomal membrane, the functioning of isolated rat liver mitochondria, and the survival of MCF-7 breast adenocarcinoma cells. It was demonstrated that alkyltriphenylphosphonium esters of phenolic acids in contrast to their parental compounds, increase liposome membrane permeability to sulforhodamine B without altering their phase state. These derivatives also exhibit uncoupling effects on oxidative phosphorylation, reducing membrane potential and stimulating oxygen consumption in mitochondria fueled by glutamate/malate (substrate for complex I of the respiratory chain) or succinate (substrate for complex II). In addition, the compounds reduced the ability of mitochondria to uptake and retain Ca2+, suggesting their influence on calcium homeostasis. Conjugation of phenolic acids with the TPP+ moiety significantly enhanced their cytotoxic effects on MCF-7 cells. This study establishes a clear structure-activity relationship, demonstrating that conjugation with TPP+ via an ester linker is an advantageous strategy for enhancing the mitochondrial targeting and bioactivity of phenolic acids compared to amide linkage or the parental compounds.
{"title":"Study of the effects of phenolic acids and their triphenylphosphonium derivatives on the permeability and state of liposomal membrane, the functional activity of isolated rat liver mitochondria, and the survival of MCF-7 cells","authors":"Mikhail V. Dubinin , Anna I. Ilzorkina , Anastasia D. Igoshkina , Natalia V. Mikina , Rezeda R. Khalitova , Nikita V. Penkov , Natalia V. Belosludtseva , Anna Y. Spivak , Konstantin N. Belosludtsev","doi":"10.1016/j.bbamem.2025.184473","DOIUrl":"10.1016/j.bbamem.2025.184473","url":null,"abstract":"<div><div>This study shows the effects of phenolic acids (gallic, coumaric, caffeic, and ferulic) and their triphenylphosphonium (TPP<sup>+</sup>) derivatives on the state of liposomal membrane, the functioning of isolated rat liver mitochondria, and the survival of MCF-7 breast adenocarcinoma cells. It was demonstrated that alkyltriphenylphosphonium esters of phenolic acids in contrast to their parental compounds, increase liposome membrane permeability to sulforhodamine B without altering their phase state. These derivatives also exhibit uncoupling effects on oxidative phosphorylation, reducing membrane potential and stimulating oxygen consumption in mitochondria fueled by glutamate/malate (substrate for complex I of the respiratory chain) or succinate (substrate for complex II). In addition, the compounds reduced the ability of mitochondria to uptake and retain Ca<sup>2+</sup>, suggesting their influence on calcium homeostasis. Conjugation of phenolic acids with the TPP<sup>+</sup> moiety significantly enhanced their cytotoxic effects on MCF-7 cells. This study establishes a clear structure-activity relationship, demonstrating that conjugation with TPP<sup>+</sup> via an ester linker is an advantageous strategy for enhancing the mitochondrial targeting and bioactivity of phenolic acids compared to amide linkage or the parental compounds.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184473"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290780","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}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.bbamem.2025.184485
Chamari S. Wijesooriya , Sharifur Rahman , Emily A. Smith
The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that interacts with different ligands, including the amyloid-beta (Aβ) peptides, to initiate signaling pathways and create pro-inflammatory mediators. Receptor diffusion plays an important role in its functionality; for example, lateral mobility is needed for the assembly of signaling complexes. However, the effect of Aβ ligand binding on the diffusion of RAGE and its correlation with RAGE-mediated signaling have not been studied. This study investigated the impact of Aβ 1–40 and Aβ 1–42 on RAGE's lateral diffusion and MAPK signaling. Differing in length by only two amino acids, these two most prominent Aβ isoforms have differing cellular toxicities: Aβ 1–42 is considered the more toxic form. Single-particle tracking measurements showed that both Aβ 1–40 and Aβ 1–42 altered RAGE diffusion in HEK293 cells compared to a ligand untreated control, although the effects were different for each peptide. Aβ 1–42 treatment enhanced the activation of both p38 and p44/42 MAPKs via RAGE, whereas Aβ 1–40 treatment did not significantly increase p38 activation. These results are consistent with the greater toxicity of Aβ 1–42: p38 MAPK is often associated with stress-stimuli and inflammation whereas p44/42 MAPK is more commonly associated with growth factors and cell proliferation. The results show that differing cellular toxicities of Aβ 1–40 and Aβ 1–42 are also associated with divergent effects on RAGE diffusion and MAPK signal pathway activation.
{"title":"Effect of amyloid-beta 1–40 and 1–42 peptides on the lateral diffusion and signaling of receptor for advanced glycation endproducts (RAGE)","authors":"Chamari S. Wijesooriya , Sharifur Rahman , Emily A. Smith","doi":"10.1016/j.bbamem.2025.184485","DOIUrl":"10.1016/j.bbamem.2025.184485","url":null,"abstract":"<div><div>The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that interacts with different ligands, including the amyloid-beta (Aβ) peptides, to initiate signaling pathways and create pro-inflammatory mediators. Receptor diffusion plays an important role in its functionality; for example, lateral mobility is needed for the assembly of signaling complexes. However, the effect of Aβ ligand binding on the diffusion of RAGE and its correlation with RAGE-mediated signaling have not been studied. This study investigated the impact of Aβ 1–40 and Aβ 1–42 on RAGE's lateral diffusion and MAPK signaling. Differing in length by only two amino acids, these two most prominent Aβ isoforms have differing cellular toxicities: Aβ 1–42 is considered the more toxic form. Single-particle tracking measurements showed that both Aβ 1–40 and Aβ 1–42 altered RAGE diffusion in HEK293 cells compared to a ligand untreated control, although the effects were different for each peptide. Aβ 1–42 treatment enhanced the activation of both p38 and p44/42 MAPKs via RAGE, whereas Aβ 1–40 treatment did not significantly increase p38 activation. These results are consistent with the greater toxicity of Aβ 1–42: p38 MAPK is often associated with stress-stimuli and inflammation whereas p44/42 MAPK is more commonly associated with growth factors and cell proliferation. The results show that differing cellular toxicities of Aβ 1–40 and Aβ 1–42 are also associated with divergent effects on RAGE diffusion and MAPK signal pathway activation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184485"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572673","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}
Pub Date : 2026-01-01Epub Date: 2025-11-18DOI: 10.1016/j.bbamem.2025.184484
Emad Ghazizadeh , Mahdi Zeidi , Wylie Stroberg
The endoplasmic reticulum (ER) is a highly dynamic organelle that undergoes continuous remodeling between tubular and sheet-like structures, driven by curvature-inducing proteins and membrane mechanics. Understanding the physical principles underlying ER shape transitions is crucial for elucidating its role in cellular homeostasis and disease. In this study, we use a mesoscopic model of membrane-protein interactions to investigate how intrinsic curvature, protein concentration, and membrane stiffening collectively regulate ER tubulation. Our results demonstrate that the critical concentration for tubulation depends nonlinearly on intrinsic curvature due to a competition between adsorption and remodeling ability. Additionally, increased membrane stiffness upon protein adsorption enhances tubulation efficiency at lower intrinsic curvatures and changes tubule geometry at higher intrinsic curvatures. Phase diagrams are constructed to map the conditions necessary for membrane remodeling, revealing critical protein concentration thresholds for ER transformation. These findings provide a quantitative framework for ER shape regulation, offering insights into how different curvature-inducing proteins coordinate ER morphogenesis.
{"title":"Tubulation of membrane sheets by curvature-inducing proteins","authors":"Emad Ghazizadeh , Mahdi Zeidi , Wylie Stroberg","doi":"10.1016/j.bbamem.2025.184484","DOIUrl":"10.1016/j.bbamem.2025.184484","url":null,"abstract":"<div><div>The endoplasmic reticulum (ER) is a highly dynamic organelle that undergoes continuous remodeling between tubular and sheet-like structures, driven by curvature-inducing proteins and membrane mechanics. Understanding the physical principles underlying ER shape transitions is crucial for elucidating its role in cellular homeostasis and disease. In this study, we use a mesoscopic model of membrane-protein interactions to investigate how intrinsic curvature, protein concentration, and membrane stiffening collectively regulate ER tubulation. Our results demonstrate that the critical concentration for tubulation depends nonlinearly on intrinsic curvature due to a competition between adsorption and remodeling ability. Additionally, increased membrane stiffness upon protein adsorption enhances tubulation efficiency at lower intrinsic curvatures and changes tubule geometry at higher intrinsic curvatures. Phase diagrams are constructed to map the conditions necessary for membrane remodeling, revealing critical protein concentration thresholds for ER transformation. These findings provide a quantitative framework for ER shape regulation, offering insights into how different curvature-inducing proteins coordinate ER morphogenesis.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184484"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562584","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}
Pub Date : 2026-01-01Epub Date: 2025-10-06DOI: 10.1016/j.bbamem.2025.184471
Agnieszka Chytła , Agnieszka Biernatowska , Weronika Gajdzik-Nowak , Aleksander F. Sikorski , Aleksander Czogalla
Membrane palmitoylated protein 1 (MPP1), a protein found to directly interact with flotillins, has been shown to play a crucial role as a raft-capturing molecule, modulating dynamics of flotillin-nanodomains and affects plasma membrane (PM) organisation in native erythroid cells. This study aims to reconstitute the flotillin-MPP1 complexes in a minimal membrane-based system to check its ability to govern domain formation and modulate fluidity and phase separation of membranes comprising simple ternary lipid mixtures. Using recombinant flotillins reconstituted into giant unilamellar vesicles (GUVs) and fluorescence lifetime imaging (FLIM), we have shown that MPP1 promotes membrane remodelling and triggers the coexistence of liquid-ordered (Lo) and liquid-disordered (Ld) domains. Additionally, we examined whether palmitoylation of MPP1 affects lipid bilayers and demonstrated that it exerts a certain influence on membrane organisation. Our data highlights that flotillin-MPP1 assemblies are sufficient and necessary to modulate the lateral organisation of lipid bilayers, pointing to their crucial role in PM organisation. Additionally, we propose a new toolset for successful flotillin reconstitution in GUVs, which is a viable platform compatible with a wide spectrum of flotillin-based studies on model membrane systems.
{"title":"MPP1 controls lipid domain remodelling in giant vesicles containing reconstituted flotillins","authors":"Agnieszka Chytła , Agnieszka Biernatowska , Weronika Gajdzik-Nowak , Aleksander F. Sikorski , Aleksander Czogalla","doi":"10.1016/j.bbamem.2025.184471","DOIUrl":"10.1016/j.bbamem.2025.184471","url":null,"abstract":"<div><div>Membrane palmitoylated protein 1 (MPP1), a protein found to directly interact with flotillins, has been shown to play a crucial role as a raft-capturing molecule, modulating dynamics of flotillin-nanodomains and affects plasma membrane (PM) organisation in native erythroid cells. This study aims to reconstitute the flotillin-MPP1 complexes in a minimal membrane-based system to check its ability to govern domain formation and modulate fluidity and phase separation of membranes comprising simple ternary lipid mixtures. Using recombinant flotillins reconstituted into giant unilamellar vesicles (GUVs) and fluorescence lifetime imaging (FLIM), we have shown that MPP1 promotes membrane remodelling and triggers the coexistence of liquid-ordered (L<sub>o</sub>) and liquid-disordered (L<sub>d</sub>) domains. Additionally, we examined whether palmitoylation of MPP1 affects lipid bilayers and demonstrated that it exerts a certain influence on membrane organisation. Our data highlights that flotillin-MPP1 assemblies are sufficient and necessary to modulate the lateral organisation of lipid bilayers, pointing to their crucial role in PM organisation. Additionally, we propose a new toolset for successful flotillin reconstitution in GUVs, which is a viable platform compatible with a wide spectrum of flotillin-based studies on model membrane systems.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184471"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145249414","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}
Pub Date : 2026-01-01Epub Date: 2025-10-20DOI: 10.1016/j.bbamem.2025.184477
Eric Umehara , Carlos Henrique T. dos Santos , Laura F. da Silva , Fernanda Thevenard , André G. Tempone , Matheus E. Rosa , Luciano Caseli , João Henrique G. Lago
This study evaluated the antiprotozoal activity of viscidone, an acetophenone isolated from Baccharis retusa, against trypomastigote forms of Trypanosoma cruzi. Viscidone showed potent antiparasitic effects (EC₅₀ = 21.3 ± 1.4 μM), comparable to benznidazole, and exhibited no cytotoxicity toward NCTC mammalian cells (CC₅₀ > 200 μM), resulting in a selectivity index (SI) higher than 9.4. To explore its mechanism of action, biophysical analyses using DPPE Langmuir monolayers as biomimetic membranes revealed that viscidone strongly interacts with lipid interfaces - expanding monolayers, decreasing compressional and viscoelastic moduli, and inducing microdomain formation, as observed by Brewster angle microscopy. These results indicate that viscidone disrupts PE-rich lipid domains, a hallmark of protozoan membranes. Its ability to insert into lipid layers under high surface pressures and its synergistic behavior with the membrane matrix support membrane perturbation as a likely mechanism underlying its antiparasitic effect. Overall, this multidisciplinary study identifies viscidone as a promising lead for antitrypanosomal drug development and highlights the value of membrane biophysics in antiparasitic research.
{"title":"Exploring the antitrypanosomal activity of viscidone, an acetophenone derivative from Baccharis retusa (Asteraceae), using biomembrane models","authors":"Eric Umehara , Carlos Henrique T. dos Santos , Laura F. da Silva , Fernanda Thevenard , André G. Tempone , Matheus E. Rosa , Luciano Caseli , João Henrique G. Lago","doi":"10.1016/j.bbamem.2025.184477","DOIUrl":"10.1016/j.bbamem.2025.184477","url":null,"abstract":"<div><div>This study evaluated the antiprotozoal activity of viscidone, an acetophenone isolated from <em>Baccharis retusa</em>, against trypomastigote forms of <em>Trypanosoma cruzi</em>. Viscidone showed potent antiparasitic effects (EC₅₀ = 21.3 ± 1.4 μM), comparable to benznidazole, and exhibited no cytotoxicity toward NCTC mammalian cells (CC₅₀ > 200 μM), resulting in a selectivity index (SI) higher than 9.4. To explore its mechanism of action, biophysical analyses using DPPE Langmuir monolayers as biomimetic membranes revealed that viscidone strongly interacts with lipid interfaces - expanding monolayers, decreasing compressional and viscoelastic moduli, and inducing microdomain formation, as observed by Brewster angle microscopy. These results indicate that viscidone disrupts PE-rich lipid domains, a hallmark of protozoan membranes. Its ability to insert into lipid layers under high surface pressures and its synergistic behavior with the membrane matrix support membrane perturbation as a likely mechanism underlying its antiparasitic effect. Overall, this multidisciplinary study identifies viscidone as a promising lead for antitrypanosomal drug development and highlights the value of membrane biophysics in antiparasitic research.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184477"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145336424","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}
Pub Date : 2026-01-01Epub Date: 2025-11-19DOI: 10.1016/j.bbamem.2025.184486
L. Stefania Vargas-Velez, Florencia Hellriegel , Mariela R. Monti, Natalia Wilke
Polybia-MP1 is an antimicrobial peptide with broad-spectrum activity, but with varying efficacy against different bacterial strains. It is proposed to act on the cell membrane, and therefore, the higher tolerance of some strains may be attributed to differences in their membrane properties. Considering this hypothesis, we studied the biophysical properties of the membrane for bacteria with different susceptibility to the peptide. We found that high tolerance to the peptide correlates with lipid membranes of high microviscosity and stiffness, factors that in turn depend on lipid packing. We propose that high lipid packing slows peptide penetration into membranes and the subsequent disruption of the bilayer, limiting its action. Therefore, we conclude that lipid packing is an important factor determining the differences in susceptibility among bacteria. This interplay between peptide action and membrane properties hinders the development of bacterial resistance to the peptide, since alterations in lipid composition lead to various changes in membrane properties, which in turn have differential effects on cell function.
{"title":"Bacterial cell susceptibility to the antimicrobial peptide MP1 depends on membrane lipid packing","authors":"L. Stefania Vargas-Velez, Florencia Hellriegel , Mariela R. Monti, Natalia Wilke","doi":"10.1016/j.bbamem.2025.184486","DOIUrl":"10.1016/j.bbamem.2025.184486","url":null,"abstract":"<div><div>Polybia-MP1 is an antimicrobial peptide with broad-spectrum activity, but with varying efficacy against different bacterial strains. It is proposed to act on the cell membrane, and therefore, the higher tolerance of some strains may be attributed to differences in their membrane properties. Considering this hypothesis, we studied the biophysical properties of the membrane for bacteria with different susceptibility to the peptide. We found that high tolerance to the peptide correlates with lipid membranes of high microviscosity and stiffness, factors that in turn depend on lipid packing. We propose that high lipid packing slows peptide penetration into membranes and the subsequent disruption of the bilayer, limiting its action. Therefore, we conclude that lipid packing is an important factor determining the differences in susceptibility among bacteria. This interplay between peptide action and membrane properties hinders the development of bacterial resistance to the peptide, since alterations in lipid composition lead to various changes in membrane properties, which in turn have differential effects on cell function.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184486"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562492","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}
Pub Date : 2026-01-01Epub Date: 2025-11-07DOI: 10.1016/j.bbamem.2025.184479
Mariana Biscaia-Caleiras , Ana Sofia Lourenço , João Nuno Moreira , Sérgio Simões
{"title":"Corrigendum to “Unveiling the impact of membrane fluidity in shaping lipid-based drug delivery systems development.” [Biochim. Biophys. Acta (BBA) – Biomembr. Volume 1868, Issue 1, January 2026, 184461]","authors":"Mariana Biscaia-Caleiras , Ana Sofia Lourenço , João Nuno Moreira , Sérgio Simões","doi":"10.1016/j.bbamem.2025.184479","DOIUrl":"10.1016/j.bbamem.2025.184479","url":null,"abstract":"","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184479"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145470391","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}
Pub Date : 2026-01-01Epub Date: 2025-10-31DOI: 10.1016/j.bbamem.2025.184480
Kevin F. dos Santos , Luciano Caseli
The entry of SARS-CoV-2 into host cells primarily involves binding of the viral spike (S) protein to the angiotensin-converting enzyme 2 (ACE2) receptor and subsequent fusion of the viral envelope with the host membrane, a process facilitated by host proteases such as transmembrane serine protease 2 (TMPRSS2). Lipid raft domains are believed to influence this internalization pathway, although the precise localization and functional roles of ACE2 and TMPRSS2 within these domains remain unclear. In this study, we employed mixed Langmuir monolayers—representing the plasma membrane (PM) and two lipid raft models (LR and Chol/SM)—to investigate the interfacial behavior of ACE2 and TMPRSS2 fragments. Using tensiometric, microscopic, and spectroscopic techniques, we found that both proteins were more readily incorporated into fluid and loosely packed monolayers (PM and LR), leading to increased molecular area and disruption of lipid organization. In contrast, the tightly packed Chol/SM monolayer exhibited minimal changes, indicating limited protein insertion. These results demonstrate that monolayer composition and packing significantly influence protein incorporation and arrangement, which may in turn affect their accessibility to viral components. Although lipid rafts are proposed sites of ACE2 and TMPRSS2 enrichment, our findings suggest that their structural organization within such domains may be modulated by the physicochemical properties of the surrounding lipid environment, with potential implications for SARS-CoV-2 infection mechanisms.
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