Pub Date : 2024-11-02DOI: 10.1016/j.chemphyslip.2024.105450
Elena A Golysheva, Denis S Baranov, Sergei A Dzuba
Lipid rafts are lipid-cholesterol nanostructures thought to exist in cell membranes, which are characterized by higher ordering compared to their surroundings. Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) have a high affinity for phospholipid membranes and can alter their structure and biological properties. Here we use electron paramagnetic resonance (EPR) in its pulsed electron spin echo (ESE) version to study spin-labeled ibuprofen (ibuprofen-SL) in a raft-mimicking bilayer, which consists of an equimolar mixture of the phospholipids dioleoyl-glycero-phosphocholine (DOPC) and dipalmitoyl-glycero-phosphocholine (DPPC), with cholesterol added in various proportions. ESE decays are sensitive to the presence of low-temperature small-angle orientational motions of molecules - stochastic molecular librations. The data obtained show that in the presence of lipid rafts the temperature dependence of the spin relaxation rate induced by this motion reaches a plateau. This behavior is characteristic of non-cooperative motion of a molecule bound to some structure denser than the rest of the medium. Based on this analogy, the data obtained were interpreted as evidence that ibuprofen-SL molecules are adsorbed on the raft boundaries.
{"title":"Evidence for capture of spin-labeled ibuprofen drug molecules by lipid rafts in model membranes.","authors":"Elena A Golysheva, Denis S Baranov, Sergei A Dzuba","doi":"10.1016/j.chemphyslip.2024.105450","DOIUrl":"10.1016/j.chemphyslip.2024.105450","url":null,"abstract":"<p><p>Lipid rafts are lipid-cholesterol nanostructures thought to exist in cell membranes, which are characterized by higher ordering compared to their surroundings. Ibuprofen and other non-steroidal anti-inflammatory drugs (NSAIDs) have a high affinity for phospholipid membranes and can alter their structure and biological properties. Here we use electron paramagnetic resonance (EPR) in its pulsed electron spin echo (ESE) version to study spin-labeled ibuprofen (ibuprofen-SL) in a raft-mimicking bilayer, which consists of an equimolar mixture of the phospholipids dioleoyl-glycero-phosphocholine (DOPC) and dipalmitoyl-glycero-phosphocholine (DPPC), with cholesterol added in various proportions. ESE decays are sensitive to the presence of low-temperature small-angle orientational motions of molecules - stochastic molecular librations. The data obtained show that in the presence of lipid rafts the temperature dependence of the spin relaxation rate induced by this motion reaches a plateau. This behavior is characteristic of non-cooperative motion of a molecule bound to some structure denser than the rest of the medium. Based on this analogy, the data obtained were interpreted as evidence that ibuprofen-SL molecules are adsorbed on the raft boundaries.</p>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566843","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 : 2024-11-01DOI: 10.1016/j.chemphyslip.2024.105449
Pedro Henrique Dos Santos Dantas, Vinícius Alexandre Fiaia Costa, Andrei Giacchetto Felice, Eduarda Guimarães Sousa, Amanda de Oliveira Matos, Siomar de Castro Soares, Marcelle Silva-Sales, Bruno Junior-Neves, Helioswilton Sales-Campos
The triggering receptor expressed on myeloid cells 2 (TREM2) is an immunoreceptor that interacts with a wide range of non-protein ligands, and it has been implicated in infectious and non-infectious diseases. However, there is a limited understanding on how this receptor interacts with non-protein ligands and the potential of such information to develop new therapeutic drugs. Therefore, our study aimed to elucidate the interactions between TREM2 and its non-protein ligands. First, we searched PubChem and Protein Data Bank (PDB) for TREM2 structures and their corresponding non-protein ligands. Subsequently, these structures were employed in molecular docking and MM/GBSA simulations with the Maestro software and molecular dynamics in GROMACS software. TREM2 was subsequently subjected to druggable site prediction using CavityPlus and receptor-based drug repositioning via the DrugRep server. TREM2 interacts with high affinity with its 12 non-protein ligands, with affinity values ranging from -33.01 kcal/mol for phosphatidylserine to -80.87 kcal/mol for cardiolipin (CLP). In molecular dynamics simulations, homodimeric TREM2 bound more stably to its lipid ligands, such as CLP and PSF, whereas it was unstable when unbound. The interactions between the receptor and its non-protein ligands were driven by the complementarity determining regions (CDR) 1 and 2, that are present in the hydrophobic and positively charged regions, highlighting that the Y38-R98 region is fundamental for drugs targeting TREM2. Our data underscore the significance of TREM2's CDRs in recognizing its ligands, suggesting they as promising targets for prospective drug design studies.
{"title":"Exploring the orphan immune receptor TREM2 and its non-protein ligands: In silico characterization.","authors":"Pedro Henrique Dos Santos Dantas, Vinícius Alexandre Fiaia Costa, Andrei Giacchetto Felice, Eduarda Guimarães Sousa, Amanda de Oliveira Matos, Siomar de Castro Soares, Marcelle Silva-Sales, Bruno Junior-Neves, Helioswilton Sales-Campos","doi":"10.1016/j.chemphyslip.2024.105449","DOIUrl":"10.1016/j.chemphyslip.2024.105449","url":null,"abstract":"<p><p>The triggering receptor expressed on myeloid cells 2 (TREM2) is an immunoreceptor that interacts with a wide range of non-protein ligands, and it has been implicated in infectious and non-infectious diseases. However, there is a limited understanding on how this receptor interacts with non-protein ligands and the potential of such information to develop new therapeutic drugs. Therefore, our study aimed to elucidate the interactions between TREM2 and its non-protein ligands. First, we searched PubChem and Protein Data Bank (PDB) for TREM2 structures and their corresponding non-protein ligands. Subsequently, these structures were employed in molecular docking and MM/GBSA simulations with the Maestro software and molecular dynamics in GROMACS software. TREM2 was subsequently subjected to druggable site prediction using CavityPlus and receptor-based drug repositioning via the DrugRep server. TREM2 interacts with high affinity with its 12 non-protein ligands, with affinity values ranging from -33.01 kcal/mol for phosphatidylserine to -80.87 kcal/mol for cardiolipin (CLP). In molecular dynamics simulations, homodimeric TREM2 bound more stably to its lipid ligands, such as CLP and PSF, whereas it was unstable when unbound. The interactions between the receptor and its non-protein ligands were driven by the complementarity determining regions (CDR) 1 and 2, that are present in the hydrophobic and positively charged regions, highlighting that the Y38-R98 region is fundamental for drugs targeting TREM2. Our data underscore the significance of TREM2's CDRs in recognizing its ligands, suggesting they as promising targets for prospective drug design studies.</p>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142566844","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 : 2024-10-09DOI: 10.1016/j.chemphyslip.2024.105448
Diyar Altun , Per Larsson , Christel A.S. Bergström , Shakhawath Hossain
The stratum corneum (SC) plays the most important role in the absorption of topical and transdermal drugs. In this study, we developed a multi-layered SC model using coarse-grained molecular dynamics (CGMD) simulations of ceramides, cholesterol, and fatty acids in equimolar proportions, starting from two different initial configurations. In the first approach, all ceramide molecules were initially in the hairpin conformation, and the membrane bilayers were pre-formed. In the second approach, ceramide molecules were introduced in either the hairpin or splayed conformation, with the lipid molecules randomly oriented at the start of the simulation. The aim was to evaluate the effects of lipid chain length on the structural and dynamic properties of SC. By incorporating ceramides and fatty acids of different chain lengths, we simulated the SC membrane in healthy and diseased states. We calculated key structural properties including the thickness, normalized lipid area, lipid tail order parameters, and spatial ordering of the lipids from each system. The results showed that systems with higher ordering and structural integrity contained an equimolar ratio of ceramides (chain length of 24 carbon atoms), fatty acids with chain lengths ≥ of 20 carbon atoms, and cholesterol. In these systems, strong apolar interactions between the ceramide and fatty acid long acyl chains restricted the mobility of the lipid molecules, thereby maintaining a compact lipid headgroup region and high order in the lipid tail region. The simulations also revealed distinct flip-flop mechanisms for cholesterol and fatty acid within the multi-layered membrane. Cholesterol is mostly diffused through the tail-tail interface region of the membrane and could flip-flop in the same bilayer. In contrast, fatty acids flip-flopped between adjacent leaflets of two bilayers in which the tails crossed the thinner headgroup region of the membrane. To conclude, our SC model provides mechanistic insights into lipid mobility and is flexible in its design and composition of different lipids, enabling studies of varying skin conditions.
{"title":"Molecular dynamics simulations of lipid composition and its impact on structural and dynamic properties of skin membrane","authors":"Diyar Altun , Per Larsson , Christel A.S. Bergström , Shakhawath Hossain","doi":"10.1016/j.chemphyslip.2024.105448","DOIUrl":"10.1016/j.chemphyslip.2024.105448","url":null,"abstract":"<div><div>The stratum corneum (SC) plays the most important role in the absorption of topical and transdermal drugs. In this study, we developed a multi-layered SC model using coarse-grained molecular dynamics (CGMD) simulations of ceramides, cholesterol, and fatty acids in equimolar proportions, starting from two different initial configurations. In the first approach, all ceramide molecules were initially in the hairpin conformation, and the membrane bilayers were pre-formed. In the second approach, ceramide molecules were introduced in either the hairpin or splayed conformation, with the lipid molecules randomly oriented at the start of the simulation. The aim was to evaluate the effects of lipid chain length on the structural and dynamic properties of SC. By incorporating ceramides and fatty acids of different chain lengths, we simulated the SC membrane in healthy and diseased states. We calculated key structural properties including the thickness, normalized lipid area, lipid tail order parameters, and spatial ordering of the lipids from each system. The results showed that systems with higher ordering and structural integrity contained an equimolar ratio of ceramides (chain length of 24 carbon atoms), fatty acids with chain lengths ≥ of 20 carbon atoms, and cholesterol. In these systems, strong apolar interactions between the ceramide and fatty acid long acyl chains restricted the mobility of the lipid molecules, thereby maintaining a compact lipid headgroup region and high order in the lipid tail region. The simulations also revealed distinct flip-flop mechanisms for cholesterol and fatty acid within the multi-layered membrane. Cholesterol is mostly diffused through the tail-tail interface region of the membrane and could flip-flop in the same bilayer. In contrast, fatty acids flip-flopped between adjacent leaflets of two bilayers in which the tails crossed the thinner headgroup region of the membrane. To conclude, our SC model provides mechanistic insights into lipid mobility and is flexible in its design and composition of different lipids, enabling studies of varying skin conditions.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142386836","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 : 2024-10-05DOI: 10.1016/j.chemphyslip.2024.105446
Somayeh Ghiasi Hafezi , Bahareh Behkamal , Mohammad Rashidmayvan , Marzieh Hosseini , Mehran Yadegari , Sahar Ghoflchi , Amin Mansoori , Mark Ghamsary , Gordon Ferns , Mohammad Reza Saberi , Habibollah Esmaily , Majid Ghayour-Mobarhan
Introduction
Elevated levels of low-density lipoprotein-cholesterol (LDL-C) is a significant risk factor for the development of cardiovascular diseases (CVD)s. Furthermore, studies have revealed an association between indices of the complete blood count (CBC) and dyslipidemia. We aimed to investigate the relationship between CBC parameters and serum levels of LDL.
Method
In a prospective study involving 9704 participants aged 35–65 years, comprehensive screening was conducted to estimate LDL-C levels and CBC indicators. The association between these biomarkers and high LDL-C (LDL-C≥130 mg/dL (3.25 mmol/L)) was investigated using various analytical methods, including Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) methodologies.
Result
The present study found that age, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), lymphocyte (LYM), PLT-LYM ratio (PLR), PLT-High-Density Lipoprotein (HDL) ratio (PHR), HGB-LYM ratio (HLR), red blood cell count (RBC), Neutrophil-HDL ratio (NHR), and PLT-RBC ratio (PRR) were all statistically significant between the two groups (p<0.05). Another important finding was that red cell distribution width (RDW) was a significant predictor for higher LDL levels in women. Furthermore, in men, RDW-PLT ratio (RPR) and PHR were the most important indicators for assessing the elevated LDL levels.
Conclusion
The study found that sex increases LDL-C odds in females by 52.9 %, while age and HCT increase it by 4.1 % and 5.5 %, respectively. RPR and PHR were the most influential variables for both genders. Elevated RPR and PHR were negatively correlated with increased LDL levels in men, and RDW levels was a statistically significant factor for women. Moreover, RDW was a significant factor in women for high levels of HDL-C.
The study revealed that females have higher LDL-C levels (16 % compared to 14 % of males), with significant differences across variables like age, HGB, HCT, PLT, RLR, PHR, RBC, LYM, NHR, RPR, and key factors like RDW and SII.
{"title":"Comparison between statistical and machine learning methods to detect the hematological indices with the greatest influence on elevated serum levels of low-density lipoprotein cholesterol","authors":"Somayeh Ghiasi Hafezi , Bahareh Behkamal , Mohammad Rashidmayvan , Marzieh Hosseini , Mehran Yadegari , Sahar Ghoflchi , Amin Mansoori , Mark Ghamsary , Gordon Ferns , Mohammad Reza Saberi , Habibollah Esmaily , Majid Ghayour-Mobarhan","doi":"10.1016/j.chemphyslip.2024.105446","DOIUrl":"10.1016/j.chemphyslip.2024.105446","url":null,"abstract":"<div><h3>Introduction</h3><div>Elevated levels of low-density lipoprotein-cholesterol (LDL-C) is a significant risk factor for the development of cardiovascular diseases (CVD)s. Furthermore, studies have revealed an association between indices of the complete blood count (CBC) and dyslipidemia. We aimed to investigate the relationship between CBC parameters and serum levels of LDL.</div></div><div><h3>Method</h3><div>In a prospective study involving 9704 participants aged 35–65 years, comprehensive screening was conducted to estimate LDL-C levels and CBC indicators. The association between these biomarkers and high LDL-C (LDL-C≥130 mg/dL (3.25 mmol/L)) was investigated using various analytical methods, including Logistic Regression (LR), Decision Tree (DT), Random Forest (RF), Neural Network (NN), and Support Vector Machine (SVM) methodologies.</div></div><div><h3>Result</h3><div>The present study found that age, hemoglobin (HGB), hematocrit (HCT), platelet count (PLT), lymphocyte (LYM), PLT-LYM ratio (PLR), PLT-High-Density Lipoprotein (HDL) ratio (PHR), HGB-LYM ratio (HLR), red blood cell count (RBC), Neutrophil-HDL ratio (NHR), and PLT-RBC ratio (PRR) were all statistically significant between the two groups (p<0.05). Another important finding was that red cell distribution width (RDW) was a significant predictor for higher LDL levels in women. Furthermore, in men, RDW-PLT ratio (RPR) and PHR were the most important indicators for assessing the elevated LDL levels.</div></div><div><h3>Conclusion</h3><div>The study found that sex increases LDL-C odds in females by 52.9 %, while age and HCT increase it by 4.1 % and 5.5 %, respectively. RPR and PHR were the most influential variables for both genders. Elevated RPR and PHR were negatively correlated with increased LDL levels in men, and RDW levels was a statistically significant factor for women. Moreover, RDW was a significant factor in women for high levels of HDL-C.</div><div>The study revealed that females have higher LDL-C levels (16 % compared to 14 % of males), with significant differences across variables like age, HGB, HCT, PLT, RLR, PHR, RBC, LYM, NHR, RPR, and key factors like RDW and SII.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142379703","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 : 2024-10-04DOI: 10.1016/j.chemphyslip.2024.105447
Sayed Haidar Abbas Raza , Zixin Huang , Yimeng Pang , Ruimin Zhong , Xiangmei Li , Sameer D. Pant , Lin Luo , Hongtao Lei
In this study, a rapid detection method utilizing colloidal gold immunochromatography (CG-ICA) was developed for the detection of illegally added prednisone acetate in health foods. Initially, the preparation conditions of colloidal gold solution were optimized. The optimal potassium carbonate dosage, antibody diluent type, antibody dosage, probe labeling time, blocking time and BSA dosage were determined. Technical analysis was performed to ensure that the established CG-ICA exhibited satisfactory color development and inhibition rates. Under optimized conditions, the cut-off value of CG-ICA was 250 μg/kg. The assay demonstrated a sensitivity of 100 %, a false positive rate of 8 %, and a false negative rate of 0, indicating high specificity for prednisone acetate. The results obtained from testing actual samples were consistent with those obtained using LC-MS/MS, thereby verifying the reliability of the developed method. This method offers robust support for the rapid detection of illegally added prednisone acetate in health foods.
{"title":"Rapid screening of prednisolone acetate adulterants in health foods using colloidal gold immunochromatographic assay","authors":"Sayed Haidar Abbas Raza , Zixin Huang , Yimeng Pang , Ruimin Zhong , Xiangmei Li , Sameer D. Pant , Lin Luo , Hongtao Lei","doi":"10.1016/j.chemphyslip.2024.105447","DOIUrl":"10.1016/j.chemphyslip.2024.105447","url":null,"abstract":"<div><div>In this study, a rapid detection method utilizing colloidal gold immunochromatography (CG-ICA) was developed for the detection of illegally added prednisone acetate in health foods. Initially, the preparation conditions of colloidal gold solution were optimized. The optimal potassium carbonate dosage, antibody diluent type, antibody dosage, probe labeling time, blocking time and BSA dosage were determined. Technical analysis was performed to ensure that the established CG-ICA exhibited satisfactory color development and inhibition rates. Under optimized conditions, the cut-off value of CG-ICA was 250 μg/kg. The assay demonstrated a sensitivity of 100 %, a false positive rate of 8 %, and a false negative rate of 0, indicating high specificity for prednisone acetate. The results obtained from testing actual samples were consistent with those obtained using LC-MS/MS, thereby verifying the reliability of the developed method. This method offers robust support for the rapid detection of illegally added prednisone acetate in health foods.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142378842","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 : 2024-09-24DOI: 10.1016/j.chemphyslip.2024.105445
Md Abdullah Al Sazzad , Max Lönnfors , Baoru Yang
Milk fat globule membrane (MFGM) promotes the lateral phase separation of milk lipids and stabilizes the fat globules in milk. The composition and structures of lipids have a significant impact on physicochemical properties of MFGM, which in turn influences the digestion and absorption of milk lipids. Phospholipids (PL), sphingolipids, and cholesterol are the major lipid constituents of MFGM. While the effects of the head-group and structure of the fatty acids (FAs) on membrane properties are commonly studied, little is known on the impact of PL regioisomerism. The present study investigated the impact of phosphatidylcholine (PC) regioisomerism on lateral segregation of milk-sphingomyelin (milk-SM) as well as the influence on the interaction of milk-SM with ceramide and cholesterol in simulated membrane systems. The regioisomer pairs of four molecular species PC 16:0/18:1n-9, PC 16:0/18:2n-6, PC 16:0/18:3n-3, and PC 16:0/20:4n-6 were included in this study. The lateral segregation was determined using lifetime analysis of trans-parinaric acid (tPA) fluorescence. Thermostability of the domains was detected using steady-state anisotropy of tPA. Our results demonstrated a clear impact of PC regioisomerism on membrane properties. PC regioisomers having the unsaturated FAs at the sn-2 position enhanced the lateral segregation of milk-SM with and without the presence of ceramide and cholesterol compared to the regioiosmers having 16:0 at the sn-2 position. Furthermore, the characteristics i. e. the acyl chain length and degree of unsaturation of sn-2 FA of the PCs had a major impact on the milk-SM gel phase and the intermolecular forces between milk-SM and ceramide/cholesterol. This work is the first investigation showing the effect of PL regioisomerism on milk-SM domains, which might have significant influence on functional properties of MFGM.
{"title":"Effect of phosphatidylcholine regioisomerism on lateral segregation of milk sphingomyelin in bilayer membranes","authors":"Md Abdullah Al Sazzad , Max Lönnfors , Baoru Yang","doi":"10.1016/j.chemphyslip.2024.105445","DOIUrl":"10.1016/j.chemphyslip.2024.105445","url":null,"abstract":"<div><div>Milk fat globule membrane (MFGM) promotes the lateral phase separation of milk lipids and stabilizes the fat globules in milk. The composition and structures of lipids have a significant impact on physicochemical properties of MFGM, which in turn influences the digestion and absorption of milk lipids. Phospholipids (PL), sphingolipids, and cholesterol are the major lipid constituents of MFGM. While the effects of the head-group and structure of the fatty acids (FAs) on membrane properties are commonly studied, little is known on the impact of PL regioisomerism. The present study investigated the impact of phosphatidylcholine (PC) regioisomerism on lateral segregation of milk-sphingomyelin (milk-SM) as well as the influence on the interaction of milk-SM with ceramide and cholesterol in simulated membrane systems. The regioisomer pairs of four molecular species PC 16:0/18:1n-9, PC 16:0/18:2n-6, PC 16:0/18:3n-3, and PC 16:0/20:4n-6 were included in this study. The lateral segregation was determined using lifetime analysis of <em>trans-</em>parinaric acid (<em>tPA</em>) fluorescence. Thermostability of the domains was detected using steady-state anisotropy of <em>tPA.</em> Our results demonstrated a clear impact of PC regioisomerism on membrane properties. PC regioisomers having the unsaturated FAs at the <em>sn</em>-2 position enhanced the lateral segregation of milk-SM with and without the presence of ceramide and cholesterol compared to the regioiosmers having 16:0 at the <em>sn</em>-2 position. Furthermore, the characteristics i. e. the acyl chain length and degree of unsaturation of <em>sn</em>-2 FA of the PCs had a major impact on the milk-SM gel phase and the intermolecular forces between milk-SM and ceramide/cholesterol. This work is the first investigation showing the effect of PL regioisomerism on milk-SM domains, which might have significant influence on functional properties of MFGM.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142338140","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 : 2024-09-10DOI: 10.1016/j.chemphyslip.2024.105444
Marika Grodzicka , Sylwia Michlewska , Adam Buczkowski , Paula Ortega , Francisco Javier de la Mata , Maria Bryszewska , Maksim Ionov
The use of dendrimers as nanovectors for nucleic acids or drugs requires the understanding of their interaction with biological membranes. This study investigates the impact of 1st generation polyphenolic carbosilane dendrimers on biological and model lipid membranes using several biophysical methods. While the increase in the z-average size of DMPC/DPPG liposomes correlated with the number of caffeic acid residues included in the dendrimer structure, dendrimers that contained polyethylene glycol chains generated lower zeta potential when interacting with a liposomal membrane. The increase in the fluorescence anisotropy of DPH and TMA-DPH probes incorporated into erythrocyte membranes predicted the ability of dendrimers to affect membrane fluidity in the hydrophobic interior and hydrophilic/polar region of a lipid bilayer. The presence of caffeic acid and polyethylene glycol chains in the dendrimer structure affected the thermodynamical properties of the membrane lipid matrix.
将树枝状聚合物用作核酸或药物的纳米载体需要了解它们与生物膜的相互作用。本研究采用多种生物物理方法研究了第一代多酚碳硅烷树枝状聚合物对生物膜和模型脂膜的影响。DMPC/DPPG 脂质体 z 平均尺寸的增加与树枝状聚合物结构中含有的咖啡酸残基数量有关，而含有聚乙二醇链的树枝状聚合物在与脂质体膜相互作用时会产生较低的 zeta 电位。加入红细胞膜的 DPH 和 TMA-DPH 探针的荧光各向异性增加，这说明树枝状聚合物能够影响脂质双分子层疏水内部和亲水/极性区域的膜流动性。树枝状聚合物结构中的咖啡酸链和聚乙二醇链会影响膜脂基质的热力学性质。
{"title":"Effect of polyphenolic dendrimers on biological and artificial lipid membranes","authors":"Marika Grodzicka , Sylwia Michlewska , Adam Buczkowski , Paula Ortega , Francisco Javier de la Mata , Maria Bryszewska , Maksim Ionov","doi":"10.1016/j.chemphyslip.2024.105444","DOIUrl":"10.1016/j.chemphyslip.2024.105444","url":null,"abstract":"<div><p>The use of dendrimers as nanovectors for nucleic acids or drugs requires the understanding of their interaction with biological membranes. This study investigates the impact of 1st generation polyphenolic carbosilane dendrimers on biological and model lipid membranes using several biophysical methods. While the increase in the z-average size of DMPC/DPPG liposomes correlated with the number of caffeic acid residues included in the dendrimer structure, dendrimers that contained polyethylene glycol chains generated lower zeta potential when interacting with a liposomal membrane. The increase in the fluorescence anisotropy of DPH and TMA-DPH probes incorporated into erythrocyte membranes predicted the ability of dendrimers to affect membrane fluidity in the hydrophobic interior and hydrophilic/polar region of a lipid bilayer. The presence of caffeic acid and polyethylene glycol chains in the dendrimer structure affected the thermodynamical properties of the membrane lipid matrix.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308424000690/pdfft?md5=fc03e278a85952db1a62e469b5de1cf4&pid=1-s2.0-S0009308424000690-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243897","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}
The stratum corneum (SC) presents certain limitations for topical administration of medication, which can be overcome using penetration enhancers (PEs) such as terpene (TP). The SC is also crucial for maintaining the skin barrier and consists of two lamellar structures: the short periodicity phase (SPP) and long periodicity phase (LPP). In this study, we monitored changes in the X-ray diffraction peaks of the human SC, 30 min after TP application (neroridol, 1,8-cineol, and d-limonene). With the application of nerolidol, no significant changes were observed in the small-angle diffraction peak positions for the lamellar structure of SPP, but the integrated intensity decreased. On the contrary, when applying 1,8-cineole and d-limonene, a lower angle peak shift with broadening of the peak width of SPP diffraction peaks was observed for d-limonene than for 1,8-cineole, and the degree of peak shift and width broadening was greater for d-limonene than for 1,8-cineole. The diffraction peaks of LPP disappeared when 1,8-cineole and d-limonene were applied. These results indicate that the degree of interaction between the SC and TP differs depending on the molecular species, and d-limonene and 1,8-cineole exhibit penetration-enhancing via lamellar structure disruption of both SPP and LPP, immediately after application.
{"title":"Evaluation of molecular interaction between intercellular lipid organization in human stratum corneum and terpenes using time-resolved synchrotron X-ray diffraction","authors":"Tomonobu Uchino , Ichiro Hatta , Michiaki Nakajo , Yuna Iwano , Mayuko Okada , Ryuji Yumoto , Yasunori Miyazaki , Yoshiyuki Kagawa","doi":"10.1016/j.chemphyslip.2024.105435","DOIUrl":"10.1016/j.chemphyslip.2024.105435","url":null,"abstract":"<div><p>The stratum corneum (SC) presents certain limitations for topical administration of medication, which can be overcome using penetration enhancers (PEs) such as terpene (TP). The SC is also crucial for maintaining the skin barrier and consists of two lamellar structures: the short periodicity phase (SPP) and long periodicity phase (LPP). In this study, we monitored changes in the X-ray diffraction peaks of the human SC, 30 min after TP application (neroridol, 1,8-cineol, and d-limonene). With the application of nerolidol, no significant changes were observed in the small-angle diffraction peak positions for the lamellar structure of SPP, but the integrated intensity decreased. On the contrary, when applying 1,8-cineole and d-limonene, a lower angle peak shift with broadening of the peak width of SPP diffraction peaks was observed for d-limonene than for 1,8-cineole, and the degree of peak shift and width broadening was greater for d-limonene than for 1,8-cineole. The diffraction peaks of LPP disappeared when 1,8-cineole and d-limonene were applied. These results indicate that the degree of interaction between the SC and TP differs depending on the molecular species, and d-limonene and 1,8-cineole exhibit penetration-enhancing via lamellar structure disruption of both SPP and LPP, immediately after application.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142138858","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 : 2024-08-30DOI: 10.1016/j.chemphyslip.2024.105434
Petra Maleš , Jana Munivrana , Lea Pašalić , Barbara Pem , Danijela Bakarić
Melting of brain sphingomyelin (bSM) manifests as a broad feature in the DSC curve that encompasses the temperature range of 25 – 45 °C, with two distinguished maxima originating from the phase transitions of two the most abundant components: C24:1 (Tm,1) and C18:0 (Tm,2). While C24:1/C18:0 sphingomyelin transforms from the gel/ripple phase to the fluid/fluid phase, the dynamics of water molecules in the interfacial layer remain completely unknown. Therefore, we carried out a calorimetric (DSC), spectroscopic (temperature-dependent UV-Vis and fluorescence) and MD simulation study of bSM in the absence/presence of Laurdan® (bSM ± L) suspended in Britton-Robinson buffer with three different pH values, 4 (BRB4), 7 (BRB7) and 9 (BRB9), and of comparable ionic strength (I = 100 mM). According to DSC, m, 1 (≈ 34.5 °C/≈ 32.1 °C) and m, 2 (≈ 38.0 °C/≈ 37.2 °C) of bSM suspended in BRB4, BRB7, and BRB9 in the absence/presence of Laurdan® are found to be practically pH-independent. Turbidity-based data (UV-Vis) detected both qualitative and quantitative differences in the response of bSM suspended in BRB4/BRB7/BRB9 (m: ∼ 35 °C/32.0 ± 0.2 °C/36.4 ± 0.4), suggesting an intricate interplay of weakening of van der Waals forces between their hydrocarbon chains and of increased hydration in the polar headgroups region during melting. The temperature-dependent response of Laurdan® reported a discontinuous, pH-dependent change in the reorientation of interfacial water molecules that coincides with the melting of C24:1 lipids (on average, m (LTC/HTC): ≈ 31.8 °C/30.6 °C/30.5 °C). MD simulations elucidated the impact of Laurdan® on a change in the physicochemical properties of bSM lipids and characterized the hydrogen bond network at the interface at 20 °C and 50 °C.
{"title":"Reorientation of interfacial water molecules during melting of brain sphingomyelin is associated with the phase transition of its C24:1 sphingomyelin lipids","authors":"Petra Maleš , Jana Munivrana , Lea Pašalić , Barbara Pem , Danijela Bakarić","doi":"10.1016/j.chemphyslip.2024.105434","DOIUrl":"10.1016/j.chemphyslip.2024.105434","url":null,"abstract":"<div><p>Melting of brain sphingomyelin (bSM) manifests as a broad feature in the DSC curve that encompasses the temperature range of 25 – 45 °C, with two distinguished maxima originating from the phase transitions of two the most abundant components: C24:1 (<em>T</em><sub>m,1</sub>) and C18:0 (<em>T</em><sub>m,2</sub>). While C24:1/C18:0 sphingomyelin transforms from the gel/ripple phase to the fluid/fluid phase, the dynamics of water molecules in the interfacial layer remain completely unknown. Therefore, we carried out a calorimetric (DSC), spectroscopic (temperature-dependent UV-Vis and fluorescence) and MD simulation study of bSM in the absence/presence of Laurdan® (bSM ± L) suspended in Britton-Robinson buffer with three different pH values, 4 (BRB4), 7 (BRB7) and 9 (BRB9), and of comparable ionic strength (<em>I</em> = 100 mM). According to DSC, <span><math><mover><mrow><mi>T</mi></mrow><mo>̅</mo></mover></math></span><sub>m, 1</sub> (≈ 34.5 °C/≈ 32.1 °C) and <span><math><mover><mrow><mi>T</mi></mrow><mo>̅</mo></mover></math></span><sub>m, 2</sub> (≈ 38.0 °C/≈ 37.2 °C) of bSM suspended in BRB4, BRB7, and BRB9 in the absence/presence of Laurdan® are found to be practically pH-independent. Turbidity-based data (UV-Vis) detected both qualitative and quantitative differences in the response of bSM suspended in BRB4/BRB7/BRB9 (<span><math><mover><mrow><mi>T</mi></mrow><mo>̅</mo></mover></math></span><sub>m</sub>: ∼ 35 °C/32.0 ± 0.2 °C/36.4 ± 0.4), suggesting an intricate interplay of weakening of van der Waals forces between their hydrocarbon chains and of increased hydration in the polar headgroups region during melting. The temperature-dependent response of Laurdan® reported a discontinuous, pH-dependent change in the reorientation of interfacial water molecules that coincides with the melting of C24:1 lipids (on average, <span><math><mover><mrow><mi>T</mi></mrow><mo>̅</mo></mover></math></span><sub>m (LTC/HTC)</sub>: ≈ 31.8 °C/30.6 °C/30.5 °C). MD simulations elucidated the impact of Laurdan® on a change in the physicochemical properties of bSM lipids and characterized the hydrogen bond network at the interface at 20 °C and 50 °C.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142096976","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 : 2024-08-05DOI: 10.1016/j.chemphyslip.2024.105425
Trent R. Llewellyn , Olivia R.C. Pimentel , Kiersten D. Lenz, Makaela M. Montoya, Jessica Z. Kubicek-Sutherland
Nanodiscs are discoidal lipoproteins that have often been used as vehicles to study membrane proteins in their native configuration. Nanodiscs have been primarily made from synthetic lipids. However, nanodiscs also offer a format by which native lipids can be studied in their natural configuration. Here, we present a method to synthesize nanodiscs from bacterial total lipid extracts using the biothreat agent, Yersinia pestis, as a proof-of-concept. The creation of nanoparticles entirely composed of bacterial lipids supports membrane characterization and vaccine antigen discovery without the inherent safety concerns associated with live bacterial cells of this Tier 1 select agent pathogen.
{"title":"Nanodisc assembly from bacterial total lipid extracts","authors":"Trent R. Llewellyn , Olivia R.C. Pimentel , Kiersten D. Lenz, Makaela M. Montoya, Jessica Z. Kubicek-Sutherland","doi":"10.1016/j.chemphyslip.2024.105425","DOIUrl":"10.1016/j.chemphyslip.2024.105425","url":null,"abstract":"<div><p>Nanodiscs are discoidal lipoproteins that have often been used as vehicles to study membrane proteins in their native configuration. Nanodiscs have been primarily made from synthetic lipids. However, nanodiscs also offer a format by which native lipids can be studied in their natural configuration. Here, we present a method to synthesize nanodiscs from bacterial total lipid extracts using the biothreat agent, <em>Yersinia pestis,</em> as a proof-of-concept. The creation of nanoparticles entirely composed of bacterial lipids supports membrane characterization and vaccine antigen discovery without the inherent safety concerns associated with live bacterial cells of this Tier 1 select agent pathogen.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308424000501/pdfft?md5=fd7f79862b351006b46d2feb143ed5e8&pid=1-s2.0-S0009308424000501-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900323","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}
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