Pub Date : 2024-12-21DOI: 10.1016/j.chemphyslip.2024.105464
Ainhoa Collada , Johann Mertens , Emma Batllori-Badia , Alberto Galindo , Antonio Cruz , Jesús Pérez-Gil
Pulmonary surfactant is a membranous complex that enables breathing dynamics at the respiratory surface. Extremely low values of surface tension are achieved at end-expiration thanks to a unique mixture of lipids and proteins. In particular, the hydrophobic surfactant proteins, specially the protein SP-B, are crucial for surfactant biophysical function, in order to provide the surfactant lipid matrix with the ability to form membranous multi-layered interfacial films that sustain optimal mechanical properties. To analyse the contribution of the proteins to modulate the resistance to mechanical forces of surfactant membrane-based structures, atomic force microscopy of supported lipid bilayers has been used here to determine quantitative mechanical parameters defining the effect of the presence of proteins SP-B and/or SP-C on phospholipid membranes intended to model at least part of the structures integrated into pulmonary surfactant complexes. The results show clear differences introduced by proteins in membrane thickness, lateral packing and elasticity, providing evidence supporting protein-promoted modulating of the mechanical properties of surfactant membranes. These effects are found consistent with the behaviour of two relevant native materials: whole pulmonary surfactant isolated from porcine bronchoalveolar lavages and freshly produced human pulmonary surfactant isolated from amniotic fluid, where it is transferred from the foetal lung before the respiratory air-liquid interface has been established.
{"title":"Effect of hydrophobic proteins in modulating the mechanical properties of lung surfactant membranes","authors":"Ainhoa Collada , Johann Mertens , Emma Batllori-Badia , Alberto Galindo , Antonio Cruz , Jesús Pérez-Gil","doi":"10.1016/j.chemphyslip.2024.105464","DOIUrl":"10.1016/j.chemphyslip.2024.105464","url":null,"abstract":"<div><div>Pulmonary surfactant is a membranous complex that enables breathing dynamics at the respiratory surface. Extremely low values of surface tension are achieved at end-expiration thanks to a unique mixture of lipids and proteins. In particular, the hydrophobic surfactant proteins, specially the protein SP-B, are crucial for surfactant biophysical function, in order to provide the surfactant lipid matrix with the ability to form membranous multi-layered interfacial films that sustain optimal mechanical properties. To analyse the contribution of the proteins to modulate the resistance to mechanical forces of surfactant membrane-based structures, atomic force microscopy of supported lipid bilayers has been used here to determine quantitative mechanical parameters defining the effect of the presence of proteins SP-B and/or SP-C on phospholipid membranes intended to model at least part of the structures integrated into pulmonary surfactant complexes. The results show clear differences introduced by proteins in membrane thickness, lateral packing and elasticity, providing evidence supporting protein-promoted modulating of the mechanical properties of surfactant membranes. These effects are found consistent with the behaviour of two relevant native materials: whole pulmonary surfactant isolated from porcine bronchoalveolar lavages and freshly produced human pulmonary surfactant isolated from amniotic fluid, where it is transferred from the foetal lung before the respiratory air-liquid interface has been established.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105464"},"PeriodicalIF":3.4,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142880716","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 : 2024-11-30DOI: 10.1016/j.chemphyslip.2024.105461
Thomas Heimburg
The action potential is widely regarded as a purely electrical phenomenon. However, one also finds mechanical and thermal changes that can be observed experimentally. In particular, nerve membranes become thicker and axons contract. The spatial length of the action potential can be quite large, ranging from millimeters to many centimeters. This suggests the use of macroscopic thermodynamics methods to understand its properties. The pulse length is several orders of magnitude larger than the synaptic gap, larger than the distance of the nodes of Ranvier and even larger than the size of many neurons such as pyramidal cells or brain stem motor neurons. Here, we review the mechanical changes in nerves, we discuss theoretical possibilities to explain them and implications of a mechanical nerve pulse for neurons and for the brain. In particular, the contraction of nerves leads to the possibility of fast mechanical synapses.
{"title":"The mechanical properties of nerves, the size of the action potential, and consequences for the brain","authors":"Thomas Heimburg","doi":"10.1016/j.chemphyslip.2024.105461","DOIUrl":"10.1016/j.chemphyslip.2024.105461","url":null,"abstract":"<div><div>The action potential is widely regarded as a purely electrical phenomenon. However, one also finds mechanical and thermal changes that can be observed experimentally. In particular, nerve membranes become thicker and axons contract. The spatial length of the action potential can be quite large, ranging from millimeters to many centimeters. This suggests the use of macroscopic thermodynamics methods to understand its properties. The pulse length is several orders of magnitude larger than the synaptic gap, larger than the distance of the nodes of Ranvier and even larger than the size of many neurons such as pyramidal cells or brain stem motor neurons. Here, we review the mechanical changes in nerves, we discuss theoretical possibilities to explain them and implications of a mechanical nerve pulse for neurons and for the brain. In particular, the contraction of nerves leads to the possibility of fast mechanical synapses.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105461"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764908","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 : 2024-11-30DOI: 10.1016/j.chemphyslip.2024.105462
Santiago Fleite , Miryan Cassanello , María del Pilar Buera
Cavitation-based technologies, such as ultrasound (or acoustic cavitation, AC) and hydrodynamic cavitation (HC), are gaining interest among green processing technologies due to their cost effectiveness in operation, toxic solvent use reduction, and ability to obtain superior processed products, compared to conventional methods. Both AC and HC generate bubbles, but their effects may differ and it is difficult to make comparisons as both are based on different phenomena and are subject to different operational variables. AC is one of the most used techniques in extraction and homogenization processes at the laboratory level. However, upscaling to an industrial level is hard. On the other hand, HC is based on the passage of the liquid through a constriction (orifice plate, Venturi, throttling valve), which causes an increase in liquid velocity at the expense of local pressure, forcing the pressure around the contraction below the threshold pressure that induces the formation of cavities. Some applications of cavitation technologies, such as the production of liposomes or lipid nanoparticles (LNPs) allow the generation of delivery systems for biomedical applications.Many others (inactivation of pathogenic viruses, bacteria and algae for water purification, extraction procedures, third generation of biofuel production, green extractions) are based on the disruption of lipid membranes. There are also applications aimed at the modification of membranes (like the milk fat globule) for the development of innovative products. Process parameters, such as cavitation intensity, duration and temperature define the impact of the process on the physical, chemical, and biological characteristics of the membranes. Thus, the adequate implementation of cavitation processes requires understanding of interactions and synergistic mechanisms in complex systems and of their effects on membranes at the microscopic or molecular level. In the present work, the use of cavitation technologies for the generation of LNPs or nanostructured lipid carriers, and the effects of AC and HC treatments on several types of membrane systems (liposomes, solid lipid nanoparticles, milk fat globules, algae and bacterial membranes) are discussed, focusing on the structural and chemical modifications of lipidic structures under cavitation.
{"title":"Modifications of biological membranes, fat globules and liposomes promoted by cavitation processes. Consequences and applications","authors":"Santiago Fleite , Miryan Cassanello , María del Pilar Buera","doi":"10.1016/j.chemphyslip.2024.105462","DOIUrl":"10.1016/j.chemphyslip.2024.105462","url":null,"abstract":"<div><div>Cavitation-based technologies, such as ultrasound (or acoustic cavitation, AC) and hydrodynamic cavitation (HC), are gaining interest among green processing technologies due to their cost effectiveness in operation, toxic solvent use reduction, and ability to obtain superior processed products, compared to conventional methods. Both AC and HC generate bubbles, but their effects may differ and it is difficult to make comparisons as both are based on different phenomena and are subject to different operational variables. AC is one of the most used techniques in extraction and homogenization processes at the laboratory level. However, upscaling to an industrial level is hard. On the other hand, HC is based on the passage of the liquid through a constriction (orifice plate, Venturi, throttling valve), which causes an increase in liquid velocity at the expense of local pressure, forcing the pressure around the contraction below the threshold pressure that induces the formation of cavities. Some applications of cavitation technologies, such as the production of liposomes or lipid nanoparticles (LNPs) allow the generation of delivery systems for biomedical applications.Many others (inactivation of pathogenic viruses, bacteria and algae for water purification, extraction procedures, third generation of biofuel production, green extractions) are based on the disruption of lipid membranes. There are also applications aimed at the modification of membranes (like the milk fat globule) for the development of innovative products. Process parameters, such as cavitation intensity, duration and temperature define the impact of the process on the physical, chemical, and biological characteristics of the membranes. Thus, the adequate implementation of cavitation processes requires understanding of interactions and synergistic mechanisms in complex systems and of their effects on membranes at the microscopic or molecular level. In the present work, the use of cavitation technologies for the generation of LNPs or nanostructured lipid carriers, and the effects of AC and HC treatments on several types of membrane systems (liposomes, solid lipid nanoparticles, milk fat globules, algae and bacterial membranes) are discussed, focusing on the structural and chemical modifications of lipidic structures under cavitation.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"267 ","pages":"Article 105462"},"PeriodicalIF":3.4,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142764901","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 : 2024-11-29DOI: 10.1016/j.chemphyslip.2024.105460
Francisco J. Barrantes
Millions of years of phylogenetic evolution have shaped the crosstalk between sterols and membrane-embedded proteins. This lengthy process, which began before the appearance of eukaryotic cells, has sculpted the two types of molecules to cover a wide spectrum of structural interconnectedness, ranging from rapid touch-and-go hits of low-affinity between surfaces to stronger lock-and-key type structural contacts. The former usually involve relatively loose contacts between linear amino acid sequences on the membrane-exposed transmembrane domains of the protein, readily accessible to the sterols as they briefly visit clefts between adjacent transmembrane segments while in rapid exchange with the bulk lipid bilayer. This operational mode is probably the most ancestral one, since it was already present in primitive bacteria interacting with hopanoid lipids. At the other end of this spectrum are more complex cholesterol binding sites that have required the acquisition of complex 3D non-sequential segments of the membrane protein to establish stereochemically elaborate 3D designs complementary to the rough and smooth surfaces of the eukaryotic neutral lipid, cholesterol. This short review explores cholesterol-membrane protein interactions using membrane protein paradigms having in common their participation in intercellular communications neurotransmission, hormone signalling, amino acid/neurotransmitter transport- and in cancer.
{"title":"The pleomorphic cholesterol sensing motifs of transmembrane proteins","authors":"Francisco J. Barrantes","doi":"10.1016/j.chemphyslip.2024.105460","DOIUrl":"10.1016/j.chemphyslip.2024.105460","url":null,"abstract":"<div><div>Millions of years of phylogenetic evolution have shaped the crosstalk between sterols and membrane-embedded proteins. This lengthy process, which began before the appearance of eukaryotic cells, has sculpted the two types of molecules to cover a wide spectrum of structural interconnectedness, ranging from rapid touch-and-go hits of low-affinity between surfaces to stronger lock-and-key type structural contacts. The former usually involve relatively loose contacts between linear amino acid sequences on the membrane-exposed transmembrane domains of the protein, readily accessible to the sterols as they briefly visit clefts between adjacent transmembrane segments while in rapid exchange with the bulk lipid bilayer. This operational mode is probably the most ancestral one, since it was already present in primitive bacteria interacting with hopanoid lipids. At the other end of this spectrum are more complex cholesterol binding sites that have required the acquisition of complex 3D non-sequential segments of the membrane protein to establish stereochemically elaborate 3D designs complementary to the rough and smooth surfaces of the eukaryotic neutral lipid, cholesterol. This short review explores cholesterol-membrane protein interactions using membrane protein paradigms having in common their participation in intercellular communications neurotransmission, hormone signalling, amino acid/neurotransmitter transport- and in cancer.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105460"},"PeriodicalIF":3.4,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142757152","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 : 2024-11-23DOI: 10.1016/j.chemphyslip.2024.105459
Ainhoa Collada, Antonio Cruz, Jesús Pérez-Gil
Pulmonary surfactant (PS) is a membranous complex that coats the respiratory air-liquid interface in air-breathing animal lungs. Its main function is to minimize the surface tension at the end of expiration, what is needed for preventing alveolar collapse. Although the tension reduction capabilities of surfactant depend on the formation of air-exposed phospholipid-enriched monolayers, the interfacial surfactant films are far from simple monolayers. Surfactant surface films are dynamically interconnected to continuously secreted newly synthetized material thanks to the action of a pair of very hydrophobic proteins, termed SP-B and SP-C, which are responsible to modulate the biophysical behavior of the complex. Other proteins in the system, such as the hydrophilic SP-A and SP-D, are integrated into different surfactant structures but participate primarily in the immune defense of the lung. In spite of countless studies on the structure and chemico-physical properties of surfactant membranes, the full complexity of surfactant three-dimensional structure is far from being completely understood. Here we review some of the most useful techniques that have allowed the characterization of the PS system along the years to develop the current models interpreting surfactant structure-function relationships.
{"title":"Studying the interfacial activity and structure of pulmonary surfactant complexes","authors":"Ainhoa Collada, Antonio Cruz, Jesús Pérez-Gil","doi":"10.1016/j.chemphyslip.2024.105459","DOIUrl":"10.1016/j.chemphyslip.2024.105459","url":null,"abstract":"<div><div>Pulmonary surfactant (PS) is a membranous complex that coats the respiratory air-liquid interface in air-breathing animal lungs. Its main function is to minimize the surface tension at the end of expiration, what is needed for preventing alveolar collapse. Although the tension reduction capabilities of surfactant depend on the formation of air-exposed phospholipid-enriched monolayers, the interfacial surfactant films are far from simple monolayers. Surfactant surface films are dynamically interconnected to continuously secreted newly synthetized material thanks to the action of a pair of very hydrophobic proteins, termed SP-B and SP-C, which are responsible to modulate the biophysical behavior of the complex. Other proteins in the system, such as the hydrophilic SP-A and SP-D, are integrated into different surfactant structures but participate primarily in the immune defense of the lung. In spite of countless studies on the structure and chemico-physical properties of surfactant membranes, the full complexity of surfactant three-dimensional structure is far from being completely understood. Here we review some of the most useful techniques that have allowed the characterization of the PS system along the years to develop the current models interpreting surfactant structure-function relationships.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105459"},"PeriodicalIF":3.4,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708828","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 : 2024-11-08DOI: 10.1016/j.chemphyslip.2024.105451
Youenn Launay , Iwan Jan , Vincent Ciesielski , Lydie Hue , Mélodie Succar , Léa Fret , Thomas Guerbette , Karima Begriche , Philippe Legrand , Daniel Catheline , Manuel Vlach , Vincent Rioux
Fatty acid desaturases are key enzymes in lipid metabolism. They introduce double bonds between defined carbons of the fatty acyl chain and catalyze rate-limiting steps in the biosynthesis of polyunsaturated fatty acids. For decades, in vitro desaturase activities have been determined by using radiolabeled fatty acids as substrates, incubated with tissue or cell fractions containing membrane-bound desaturases. However, handling radioactivity is being increasingly complicated due to safety and regulatory concern. Radiolabeled fatty acids are also expensive and many of them are not commercially available. There is therefore a crucial need to develop new methods. Although methods using unlabeled fatty acids as substrates have recently been validated, they are well suited for large tissue samples and did not achieve the same sensitivity as the radioactive ones. Here, we show that negative chemical ionization GC-MS on stable isotope-labeled fatty acids, derivatized to pentafluorobenzyl esters, now offers this opportunity, because of its high sensitivity in the selected ion monitoring mode. By using this simple and affordable improved method, we measured the kinetic parameters of mouse liver Δ6-desaturase for its two main substrates (C18:2 n-6 and C18:3 n-3; 10–13 µM). Moreover, this method enabled to compare Δ5-desaturase apparent Km values (19–22 µM) for its two main substrates (C20:3 n-6 and C20:4 n-3). Finally, we re-evaluated the controversial effect of freezing on desaturase activities by using both frozen rat tissues and cryopreserved human hepatocytes. This safe, reliable and sensitive method may be applied to other enzymatic activities involving fatty acids (elongation, hydroxylation) in miniaturized samples.
{"title":"Use of stable isotope-labeled fatty acids to measure desaturase activities with negative chemical ionization GC-MS","authors":"Youenn Launay , Iwan Jan , Vincent Ciesielski , Lydie Hue , Mélodie Succar , Léa Fret , Thomas Guerbette , Karima Begriche , Philippe Legrand , Daniel Catheline , Manuel Vlach , Vincent Rioux","doi":"10.1016/j.chemphyslip.2024.105451","DOIUrl":"10.1016/j.chemphyslip.2024.105451","url":null,"abstract":"<div><div>Fatty acid desaturases are key enzymes in lipid metabolism. They introduce double bonds between defined carbons of the fatty acyl chain and catalyze rate-limiting steps in the biosynthesis of polyunsaturated fatty acids. For decades, <em>in vitro</em> desaturase activities have been determined by using radiolabeled fatty acids as substrates, incubated with tissue or cell fractions containing membrane-bound desaturases. However, handling radioactivity is being increasingly complicated due to safety and regulatory concern. Radiolabeled fatty acids are also expensive and many of them are not commercially available. There is therefore a crucial need to develop new methods. Although methods using unlabeled fatty acids as substrates have recently been validated, they are well suited for large tissue samples and did not achieve the same sensitivity as the radioactive ones. Here, we show that negative chemical ionization GC-MS on stable isotope-labeled fatty acids, derivatized to pentafluorobenzyl esters, now offers this opportunity, because of its high sensitivity in the selected ion monitoring mode. By using this simple and affordable improved method, we measured the kinetic parameters of mouse liver Δ6-desaturase for its two main substrates (C18:2 n-6 and C18:3 n-3; 10–13 µM). Moreover, this method enabled to compare Δ5-desaturase apparent Km values (19–22 µM) for its two main substrates (C20:3 n-6 and C20:4 n-3). Finally, we re-evaluated the controversial effect of freezing on desaturase activities by using both frozen rat tissues and cryopreserved human hepatocytes. This safe, reliable and sensitive method may be applied to other enzymatic activities involving fatty acids (elongation, hydroxylation) in miniaturized samples.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105451"},"PeriodicalIF":3.4,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142610800","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 : 2024-11-02DOI: 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":"<div><div>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.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105450"},"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":"<div><div>The triggering receptor expressed on myeloid cells 2 <strong>(</strong>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.</div></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"266 ","pages":"Article 105449"},"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.
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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":"265 ","pages":"Article 105446"},"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}
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