Pub Date : 2025-03-25DOI: 10.1016/j.chemphyslip.2025.105484
Daniel A. Peñalva, Juan Pablo Munafó, Silvia S. Antollini
Biological membranes are complex entities composed of various molecules exhibiting lateral and transbilayer lipid asymmetries, along with a selective spatial distribution of different membrane proteins. This dynamic orchestration is crucial for proper physiological functions, undergoes changes with aging, and is disturbed in several neurological disorders. In this review, we analyze the impact of disruption in this equilibrium on physiological aging and the onset of pathological conditions. Alzheimer´s disease (AD) is a multifactorial neurodegenerative disorder in the elderly, characterized by the increased presence of the Aβ peptide, which supports the amyloid hypothesis of the disease. However, AD also involves a progressive loss of cholinergic innervation, leading to the cholinergic hypothesis of the disease. Nicotinic acetylcholine receptors (nAChRs) are transmembrane proteins, and Aβ peptides, their oligomeric and fibrillar species, which increase in hydrophobicity as they develop, interact with membranes. Therefore, a membrane hypothesis of the disease emerges as a bridge between the other two. Here, we discuss the impact of the membrane environment, through direct or indirect mechanisms, on cholinergic signaling and Aβ formation and subsequent incorporation into the membrane, with a special focus on the crucial role of cholesterol in these processes.
{"title":"Cholesterol´s role in membrane organization and nicotinic acetylcholine receptor function: Implications for aging and Alzheimer's disease","authors":"Daniel A. Peñalva, Juan Pablo Munafó, Silvia S. Antollini","doi":"10.1016/j.chemphyslip.2025.105484","DOIUrl":"10.1016/j.chemphyslip.2025.105484","url":null,"abstract":"<div><div>Biological membranes are complex entities composed of various molecules exhibiting lateral and transbilayer lipid asymmetries, along with a selective spatial distribution of different membrane proteins. This dynamic orchestration is crucial for proper physiological functions, undergoes changes with aging, and is disturbed in several neurological disorders. In this review, we analyze the impact of disruption in this equilibrium on physiological aging and the onset of pathological conditions. Alzheimer´s disease (AD) is a multifactorial neurodegenerative disorder in the elderly, characterized by the increased presence of the Aβ peptide, which supports the amyloid hypothesis of the disease. However, AD also involves a progressive loss of cholinergic innervation, leading to the cholinergic hypothesis of the disease. Nicotinic acetylcholine receptors (nAChRs) are transmembrane proteins, and Aβ peptides, their oligomeric and fibrillar species, which increase in hydrophobicity as they develop, interact with membranes. Therefore, a membrane hypothesis of the disease emerges as a bridge between the other two. Here, we discuss the impact of the membrane environment, through direct or indirect mechanisms, on cholinergic signaling and Aβ formation and subsequent incorporation into the membrane, with a special focus on the crucial role of cholesterol in these processes.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"269 ","pages":"Article 105484"},"PeriodicalIF":3.4,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143727188","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 : 2025-03-22DOI: 10.1016/j.chemphyslip.2025.105486
Diego de Mendoza
Membrane proteins have central roles in a vast number of vital cellular processes. A common structural feature of most membrane proteins is the presence of one or more hydrophobic alpha-helices that interact with the lipid bilayer. Because of the interaction with the surrounding lipids, the organization of these helices will be sensitive to lipid properties like fluidity and hydrophobic thickness. The helices may adapt to the lipids in different ways, which in turn can influence the structure and function of the intact membrane protein. In this review article, I will focus on how the lipid environment governs the signaling state of a transmembrane protein and in how the lipid bilayer influences the catalytic and substrate channeling role of a peripheral protein.
{"title":"Membranes, where lipids and protein meet","authors":"Diego de Mendoza","doi":"10.1016/j.chemphyslip.2025.105486","DOIUrl":"10.1016/j.chemphyslip.2025.105486","url":null,"abstract":"<div><div>Membrane proteins have central roles in a vast number of vital cellular processes. A common structural feature of most membrane proteins is the presence of one or more hydrophobic alpha-helices that interact with the lipid bilayer. Because of the interaction with the surrounding lipids, the organization of these helices will be sensitive to lipid properties like fluidity and hydrophobic thickness. The helices may adapt to the lipids in different ways, which in turn can influence the structure and function of the intact membrane protein. In this review article, I will focus on how the lipid environment governs the signaling state of a transmembrane protein and in how the lipid bilayer influences the catalytic and substrate channeling role of a peripheral protein.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"268 ","pages":"Article 105486"},"PeriodicalIF":3.4,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697621","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 : 2025-03-21DOI: 10.1016/j.chemphyslip.2025.105485
Alain Bolaño Alvarez , María Elisa Mariani , Pablo E.A. Rodríguez , Gerardo D. Fidelio
Nanostructured lipid/peptide film at air/water interface allow to build different molecular arrangements depending of peptide sequence, peptide proportion and type of lipid. We studied the surface properties of Aβ(1 −42) and its retro-isomer Aβ(42 −1) amyloid peptides mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid at the air/water interface. In absence of lipids, pure form of both Aβ(1 −42) and Aβ(42 −1) form insoluble monolayer films without appreciable fibril-like structures despite the high interfacial confinement. We show the lipid/peptide interfacial organization depends on the reversing sequence peptide in lipid enriched environment. In POPC/Aβ(1 −42) mixed film we have observed network fibril-like structures. However, using Aβ(42 −1) retro-isomer peptide to form the mixed film, the induced structuration acquired an isolated fibers arrangement associated with oligomers. The above structures are clearly visualized at the interface by using Brewster Angle Microscopy. In the same way, the isolate fibers and oligomers become Thioflavin T positive when they are observed by Fluorescence Microscopy. Thus, we attributed an amyloid behavior at the air/water interface that was also evidenced by Scanning Electron Microscopy when the mixed film was transferred to mica support. Changes from an exclusive β-sheet in pure peptide to a notable increase in α-helix/unordered conformations were induced by the presence of the lipid keeping with fibril-like structures. We postulated that the amyloid fibril formation at the membrane interface not only depends on the interfacial lipid environment and the low amyloid peptide content but also by the reversing sequencing that imposed a differential lipid/peptide interaction at the interface. Despite the retro-isomer peptide has not impact nor the overall molecular hydrophobicity neither on the interfacial behavior although perform a “conformational selective process” that depends on the β-sheet and α-helix contents.
{"title":"The reverse sequence of Aβ amyloid self-triggers isolated nano-fibers and oligomers in lipid environment","authors":"Alain Bolaño Alvarez , María Elisa Mariani , Pablo E.A. Rodríguez , Gerardo D. Fidelio","doi":"10.1016/j.chemphyslip.2025.105485","DOIUrl":"10.1016/j.chemphyslip.2025.105485","url":null,"abstract":"<div><div>Nanostructured lipid/peptide film at air/water interface allow to build different molecular arrangements depending of peptide sequence, peptide proportion and type of lipid. We studied the surface properties of Aβ(1 −42) and its retro-isomer Aβ(42 −1) amyloid peptides mixed with 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) lipid at the air/water interface. In absence of lipids, pure form of both Aβ(1 −42) and Aβ(42 −1) form insoluble monolayer films without appreciable fibril-like structures despite the high interfacial confinement. We show the lipid/peptide interfacial organization depends on the reversing sequence peptide in lipid enriched environment. In POPC/Aβ(1 −42) mixed film we have observed network fibril-like structures. However, using Aβ(42 −1) retro-isomer peptide to form the mixed film, the induced structuration acquired an isolated fibers arrangement associated with oligomers. The above structures are clearly visualized at the interface by using Brewster Angle Microscopy. In the same way, the isolate fibers and oligomers become Thioflavin T positive when they are observed by Fluorescence Microscopy. Thus, we attributed an amyloid behavior at the air/water interface that was also evidenced by Scanning Electron Microscopy when the mixed film was transferred to mica support. Changes from an exclusive β-sheet in pure peptide to a notable increase in α-helix/unordered conformations were induced by the presence of the lipid keeping with fibril-like structures. We postulated that the amyloid fibril formation at the membrane interface not only depends on the interfacial lipid environment and the low amyloid peptide content but also by the reversing sequencing that imposed a differential lipid/peptide interaction at the interface. Despite the retro-isomer peptide has not impact nor the overall molecular hydrophobicity neither on the interfacial behavior although perform a <em><strong>“conformational selective process”</strong></em> that depends on the β-sheet and α-helix contents.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"268 ","pages":"Article 105485"},"PeriodicalIF":3.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143690616","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 : 2025-02-18DOI: 10.1016/j.chemphyslip.2025.105476
Trent R. Llewellyn, Olivia R.C. Pimentel, Kiersten D. Lenz, Makaela M. Montoya, Jessica Z. Kubicek-Sutherland
{"title":"Corrigendum to: “Nanodisc assembly from bacterial total lipid extracts” [Chem. Phys. Lipids (2024) 105425]","authors":"Trent R. Llewellyn, Olivia R.C. Pimentel, Kiersten D. Lenz, Makaela M. Montoya, Jessica Z. Kubicek-Sutherland","doi":"10.1016/j.chemphyslip.2025.105476","DOIUrl":"10.1016/j.chemphyslip.2025.105476","url":null,"abstract":"","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105476"},"PeriodicalIF":3.4,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456551","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}
In this study, we introduce a novel method for quantifying the mechanical properties of lipid membranes-bending rigidity (κ), Gaussian rigidity (κG), and surface tension (γ) using molecular dynamics (MD) simulations. Our approach is applied to membranes incorporating 2-hydroxyoleic acid (2OHOA), a synthetic oleic acid derivative currently under clinical investigation for its anticancer properties. 2OHOA modifies the plasma membrane composition in cancer cells and activates sphingomyelin synthase 1 (SMS1), an enzyme critical for maintaining sphingolipid levels in the plasma membrane. This research focuses on how the integration of 2OHOA into ceramide and sphingomyelin alters the mechanical and biophysical properties of these membranes. We employed MD simulations to analyze structural parameters such as lipid area, volume, and bilayer thickness. Additionally, by constructing a system of linear equations based on the Helfrich-Seifert model, we estimated the mechanical properties of hydroxylated versus non-hydroxylated membranes. Our findings reveal significant membrane rigidity and curvature changes due to hydroxylation, affecting membrane-protein interactions and cellular processes like vesiculation. This work provides critical insights into the molecular mechanisms by which hydroxylation influences membrane elasticity, with implications for both fundamental biophysics and therapeutic applications in cancer treatment.
{"title":"Bending the rules: Molecular dynamics of hydroxylated sphingolipid membranes with 2-hydroxyoleic acid","authors":"Lucia Sessa , Simona Concilio , Miriam Di Martino , Davide Romanini , Xavier Busquets , Stefano Piotto","doi":"10.1016/j.chemphyslip.2025.105475","DOIUrl":"10.1016/j.chemphyslip.2025.105475","url":null,"abstract":"<div><div>In this study, we introduce a novel method for quantifying the mechanical properties of lipid membranes-bending rigidity (κ), Gaussian rigidity (κ<sub>G</sub>), and surface tension (γ) using molecular dynamics (MD) simulations. Our approach is applied to membranes incorporating 2-hydroxyoleic acid (2OHOA), a synthetic oleic acid derivative currently under clinical investigation for its anticancer properties. 2OHOA modifies the plasma membrane composition in cancer cells and activates sphingomyelin synthase 1 (SMS1), an enzyme critical for maintaining sphingolipid levels in the plasma membrane. This research focuses on how the integration of 2OHOA into ceramide and sphingomyelin alters the mechanical and biophysical properties of these membranes. We employed MD simulations to analyze structural parameters such as lipid area, volume, and bilayer thickness. Additionally, by constructing a system of linear equations based on the Helfrich-Seifert model, we estimated the mechanical properties of hydroxylated versus non-hydroxylated membranes. Our findings reveal significant membrane rigidity and curvature changes due to hydroxylation, affecting membrane-protein interactions and cellular processes like vesiculation. This work provides critical insights into the molecular mechanisms by which hydroxylation influences membrane elasticity, with implications for both fundamental biophysics and therapeutic applications in cancer treatment.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"268 ","pages":"Article 105475"},"PeriodicalIF":3.4,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412560","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}
Pub Date : 2025-02-03DOI: 10.1016/j.chemphyslip.2025.105474
Luis Fernando do Carmo Morato , Gilia Cristine Marques Ruiz , Carlos Junior Amorim Lessa , Danilo da Silva Olivier , Marcos Serrou do Amaral , Orisson Ponce Gomes , Wallance Moreira Pazin , Augusto Batagin-Neto , Osvaldo N. Oliveira Jr , Carlos José Leopoldo Constantino
The increased use of agrochemicals in crop production raises concerns about the risk of combined pesticide exposure through water and food, potentially leading to a ‘cocktail effect’ with synergistic impacts on human health. To investigate such effects, we used the pesticides acephate and diuron interacting with a mimetic system of the cell membrane, composed of lipid monolayers. These mimetic systems were composed by a mixture of POPC, cholesterol and sphingomyelin (70/20/10 mol%), respectively, close to the composition found in mammalian membranes. Results from Langmuir monolayers, including surface pressure-area isotherms, polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM), showed that the pesticides interact predominantly with the polar head region of the lipids, a finding supported by density functional theory (DFT) calculations and molecular dynamics simulations. The cocktail had a similar effect in π-A isotherms; however, PM-IRRAS data suggests a stronger effect of the cocktail on the ternary monolayer at the molecular level, once the pesticide mixture changed the conformation and orientation of the headgroup and disturbed the hydrocarbon chain. These results evidence the impact of the ‘cocktail effect’ on lipid membranes, highlighting potential health risks associated with pesticide mixtures.
{"title":"Combined impact of pesticides on mono- and bilayer lipid membranes","authors":"Luis Fernando do Carmo Morato , Gilia Cristine Marques Ruiz , Carlos Junior Amorim Lessa , Danilo da Silva Olivier , Marcos Serrou do Amaral , Orisson Ponce Gomes , Wallance Moreira Pazin , Augusto Batagin-Neto , Osvaldo N. Oliveira Jr , Carlos José Leopoldo Constantino","doi":"10.1016/j.chemphyslip.2025.105474","DOIUrl":"10.1016/j.chemphyslip.2025.105474","url":null,"abstract":"<div><div>The increased use of agrochemicals in crop production raises concerns about the risk of combined pesticide exposure through water and food, potentially leading to a ‘cocktail effect’ with synergistic impacts on human health. To investigate such effects, we used the pesticides acephate and diuron interacting with a mimetic system of the cell membrane, composed of lipid monolayers. These mimetic systems were composed by a mixture of POPC, cholesterol and sphingomyelin (70/20/10 mol%), respectively, close to the composition found in mammalian membranes. Results from Langmuir monolayers, including surface pressure-area isotherms, polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), and Brewster angle microscopy (BAM), showed that the pesticides interact predominantly with the polar head region of the lipids, a finding supported by density functional theory (DFT) calculations and molecular dynamics simulations. The cocktail had a similar effect in π-A isotherms; however, PM-IRRAS data suggest<del>s</del> a stronger effect of the cocktail on the ternary monolayer at the molecular level, once the pesticide mixture changed the conformation and orientation of the headgroup and disturbed the hydrocarbon chain. These results evidence the impact of the ‘cocktail effect’ on lipid membranes, highlighting potential health risks associated with pesticide mixtures.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"268 ","pages":"Article 105474"},"PeriodicalIF":3.4,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254078","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 : 2025-02-01DOI: 10.1016/j.chemphyslip.2025.105473
Mariana S.S. Oliveira, Amanda C. Caritá, Karin A. Riske
Membrane solubilization by detergents is routinely performed to separate membrane components, and to extract and purify membrane proteins. This process depends both on the characteristics of the detergent and properties of the membrane. Here we investigate the interaction of eight detergents with very distinct physicochemical features with model membranes in different biologically relevant phases. The detergents chosen were the non-ionic Triton X-100, Triton X-165, C10E5, octyl glucopyranoside (OG) and dodecyl maltoside (DDM) and the ionic sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB) and Chaps. Three lipid compositions were explored: pure palmitoyl oleoyl phosphatidylcholine (POPC), in the liquid-disordered (Ld) phase, sphingomyelin (SM)/cholesterol 7:3 (chol) in the liquid-ordered (Lo) phase and the biomimetic POPC/SM/chol 2:1:2, which might exhibit Lo/Ld phase separation. Turbidity measurements of small liposomes were performed along the titration with the detergents to obtain the overall solubilization profiles and optical microscopy of giant unilamellar vesicles (GUVs) was used to reveal the mechanism of interaction of the detergents. The presence of cholesterol renders the membranes partly/fully insoluble in all detergents, and the charged detergents are the least effective to solubilize POPC. The non-ionic detergents, with exception of DDM, with the bulkiest headgroup, caused a substantial increase in surface area of POPC, which was quantified directly on single GUVs. The other detergents induced mainly vesicle burst. Detergents that caused some increase in area induced Lo/Ld phase separation in the ternary mixture, with preferential solubilization of the latter. The insoluble area fraction left intact was quantified. Overall, the non-ionic detergents were the most effective in solubilizing lipid membranes.
{"title":"Interaction of biomimetic lipid membranes with detergents with different physicochemical characteristics","authors":"Mariana S.S. Oliveira, Amanda C. Caritá, Karin A. Riske","doi":"10.1016/j.chemphyslip.2025.105473","DOIUrl":"10.1016/j.chemphyslip.2025.105473","url":null,"abstract":"<div><div>Membrane solubilization by detergents is routinely performed to separate membrane components, and to extract and purify membrane proteins. This process depends both on the characteristics of the detergent and properties of the membrane. Here we investigate the interaction of eight detergents with very distinct physicochemical features with model membranes in different biologically relevant phases. The detergents chosen were the non-ionic Triton X-100, Triton X-165, C10E5, octyl glucopyranoside (OG) and dodecyl maltoside (DDM) and the ionic sodium dodecyl sulfate (SDS), cetyl trimethyl ammonium bromide (CTAB) and Chaps. Three lipid compositions were explored: pure palmitoyl oleoyl phosphatidylcholine (POPC), in the liquid-disordered (Ld) phase, sphingomyelin (SM)/cholesterol 7:3 (chol) in the liquid-ordered (Lo) phase and the biomimetic POPC/SM/chol 2:1:2, which might exhibit Lo/Ld phase separation. Turbidity measurements of small liposomes were performed along the titration with the detergents to obtain the overall solubilization profiles and optical microscopy of giant unilamellar vesicles (GUVs) was used to reveal the mechanism of interaction of the detergents. The presence of cholesterol renders the membranes partly/fully insoluble in all detergents, and the charged detergents are the least effective to solubilize POPC. The non-ionic detergents, with exception of DDM, with the bulkiest headgroup, caused a substantial increase in surface area of POPC, which was quantified directly on single GUVs. The other detergents induced mainly vesicle burst. Detergents that caused some increase in area induced Lo/Ld phase separation in the ternary mixture, with preferential solubilization of the latter. The insoluble area fraction left intact was quantified. Overall, the non-ionic detergents were the most effective in solubilizing lipid membranes.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105473"},"PeriodicalIF":3.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078088","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 : 2025-01-09DOI: 10.1016/j.chemphyslip.2025.105471
Huiying Kong , Shanshan Liu , Zhenzhen Li , Li Xu , Kai Zhang , Yuanyin Wang
Dental fluorosis, as a common chronic fluoride toxicity oral disease, is mainly caused by long-term excessive intake of fluoride, which seriously affects the aesthetics and function of patients' teeth. In recent years, with the rapid development of metabolomics technology, lipidomics, as an important means to study the changes in lipid metabolism in organisms, has shown great potential in revealing the mechanisms of disease development. As a major component of cell membranes and a signaling molecule, metabolic disorders of lipids are closely related to a variety of diseases, but the specific mechanism of action in dental fluorosis is still unclear. Therefore, the present study aimed to systematically analyze the differences in lipid profiles between dental fluorosis patients and healthy populations by using broad-based targeted lipidomics technology to provide new perspectives on the pathogenesis of dental fluorosis. To this end, the researchers compared the salivary lipidome of healthy participants with the salivary micro lipidome of dental fluorosis patients. Their saliva samples were collected, and advanced broad-based targeted lipidomics technology, combined with a high-performance liquid chromatography-mass spectrometry (LC-MS) system, was used to comprehensively detect and quantify the lipids in the samples. The lipid data were processed and analyzed by bioinformatics to identify the unique patterns of changes in the lipid profiles of dental fluorosis patients and to verify the significance of these changes using statistical methods. Several glycerophospholipids, fatty acyls, and sphingolipids exhibited marked alterations in dental Among these, glycocholic acid, LPA (18:4), taurolithocholic acid-3-sulfate, lithocholic acid-3-sulfate, and taurochenodeoxycholic acid-3-sulfate were observed between dental fluorosis patients and healthy controls. taurochenodeoxycholic acid was significantly decreased, while PA (12:0_12:0) levels were significantly elevated. These findings suggest that These findings suggest that disturbances in lipid metabolism play a crucial role in developing dental fluorosis.
{"title":"Broad-based targeted lipidomic analysis of dental fluorosis population in an adult population","authors":"Huiying Kong , Shanshan Liu , Zhenzhen Li , Li Xu , Kai Zhang , Yuanyin Wang","doi":"10.1016/j.chemphyslip.2025.105471","DOIUrl":"10.1016/j.chemphyslip.2025.105471","url":null,"abstract":"<div><div>Dental fluorosis, as a common chronic fluoride toxicity oral disease, is mainly caused by long-term excessive intake of fluoride, which seriously affects the aesthetics and function of patients' teeth. In recent years, with the rapid development of metabolomics technology, lipidomics, as an important means to study the changes in lipid metabolism in organisms, has shown great potential in revealing the mechanisms of disease development. As a major component of cell membranes and a signaling molecule, metabolic disorders of lipids are closely related to a variety of diseases, but the specific mechanism of action in dental fluorosis is still unclear. Therefore, the present study aimed to systematically analyze the differences in lipid profiles between dental fluorosis patients and healthy populations by using broad-based targeted lipidomics technology to provide new perspectives on the pathogenesis of dental fluorosis. To this end, the researchers compared the salivary lipidome of healthy participants with the salivary micro lipidome of dental fluorosis patients. Their saliva samples were collected, and advanced broad-based targeted lipidomics technology, combined with a high-performance liquid chromatography-mass spectrometry (LC-MS) system, was used to comprehensively detect and quantify the lipids in the samples. The lipid data were processed and analyzed by bioinformatics to identify the unique patterns of changes in the lipid profiles of dental fluorosis patients and to verify the significance of these changes using statistical methods. Several glycerophospholipids, fatty acyls, and sphingolipids exhibited marked alterations in dental Among these, glycocholic acid, LPA (18:4), taurolithocholic acid-3-sulfate, lithocholic acid-3-sulfate, and taurochenodeoxycholic acid-3-sulfate were observed between dental fluorosis patients and healthy controls. taurochenodeoxycholic acid was significantly decreased, while PA (12:0_12:0) levels were significantly elevated. These findings suggest that These findings suggest that disturbances in lipid metabolism play a crucial role in developing dental fluorosis.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105471"},"PeriodicalIF":3.4,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142963388","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}
Pub Date : 2025-01-06DOI: 10.1016/j.chemphyslip.2025.105472
Jessica Rojas-Palomino , Jon Altuna-Alvarez , Amaia González-Magaña , María Queralt-Martín , David Albesa-Jové , Antonio Alcaraz
We present an in-depth electrophysiological analysis of Tse5, a pore-forming toxin (PFT) delivered by the type VI secretion system (T6SS) of Pseudomonas aeruginosa. The T6SS is a sophisticated bacterial secretion system that injects toxic effector proteins into competing bacteria or host cells, providing a competitive advantage by disabling other microbes and modulating their environment. Our findings highlight the dependency of Tse5 insertion on membrane charge and electrolyte concentration, suggesting an in vivo effect from the periplasmic space. Conductance and selectivity experiments reveal a predominant and reproducible pore architecture of Tse5, characterized by a weak cation selectivity without chemical specificity. pH titration experiments suggest a proteolipidic pore structure influenced by both protein and lipid charges, a hypothesis further supported by experiments involving engineered mutants of Tse5 with altered glycine zippers. These results significantly advance our understanding of Tse5's molecular mechanism of toxicity, paving the way for potential applications in biosensing and macromolecular delivery.
{"title":"Electrophysiological dissection of the ion channel activity of the Pseudomonas aeruginosa ionophore protein toxin Tse5","authors":"Jessica Rojas-Palomino , Jon Altuna-Alvarez , Amaia González-Magaña , María Queralt-Martín , David Albesa-Jové , Antonio Alcaraz","doi":"10.1016/j.chemphyslip.2025.105472","DOIUrl":"10.1016/j.chemphyslip.2025.105472","url":null,"abstract":"<div><div>We present an in-depth electrophysiological analysis of Tse5, a pore-forming toxin (PFT) delivered by the type VI secretion system (T6SS) of <em>Pseudomonas aeruginosa</em>. The T6SS is a sophisticated bacterial secretion system that injects toxic effector proteins into competing bacteria or host cells, providing a competitive advantage by disabling other microbes and modulating their environment. Our findings highlight the dependency of Tse5 insertion on membrane charge and electrolyte concentration, suggesting an in vivo effect from the periplasmic space. Conductance and selectivity experiments reveal a predominant and reproducible pore architecture of Tse5, characterized by a weak cation selectivity without chemical specificity. pH titration experiments suggest a proteolipidic pore structure influenced by both protein and lipid charges, a hypothesis further supported by experiments involving engineered mutants of Tse5 with altered glycine zippers. These results significantly advance our understanding of Tse5's molecular mechanism of toxicity, paving the way for potential applications in biosensing and macromolecular delivery.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105472"},"PeriodicalIF":3.4,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942103","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 : 2025-01-01DOI: 10.1016/j.chemphyslip.2024.105458
L. Stefania Vargas-Velez , Natalia Wilke
Laurdan is a valuable tool for analyzing phase transitions and general behavior in synthetic lipid membranes. Its use is very straightforward, thus, its application in cells has expanded rapidly in recent years. It has been demonstrated that Laurdan is very useful for analyzing membrane trends when cells are subjected to some treatment, or when different cell mutations are compared. However, a deep interpretation of the data is not as straightforward as in synthetic lipid bilayers. In this review, we complied results found in mammalian and bacterial cells and noted that the use of Laurdan could be improved if a comparison between publications could be done. At the moment this is not easy, mainly due to the lack of complete information in the publications, and to the different methodologies employed in the data recording and processing. We conclude that research in cell membrane topics would benefit from a better use of the Laurdan probe.
{"title":"Laurdan in living cells: Where do we stand?","authors":"L. Stefania Vargas-Velez , Natalia Wilke","doi":"10.1016/j.chemphyslip.2024.105458","DOIUrl":"10.1016/j.chemphyslip.2024.105458","url":null,"abstract":"<div><div>Laurdan is a valuable tool for analyzing phase transitions and general behavior in synthetic lipid membranes. Its use is very straightforward, thus, its application in cells has expanded rapidly in recent years. It has been demonstrated that Laurdan is very useful for analyzing membrane trends when cells are subjected to some treatment, or when different cell mutations are compared. However, a deep interpretation of the data is not as straightforward as in synthetic lipid bilayers. In this review, we complied results found in mammalian and bacterial cells and noted that the use of Laurdan could be improved if a comparison between publications could be done. At the moment this is not easy, mainly due to the lack of complete information in the publications, and to the different methodologies employed in the data recording and processing. We conclude that research in cell membrane topics would benefit from a better use of the Laurdan probe.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105458"},"PeriodicalIF":3.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142737915","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}
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