Biochimica et biophysica acta. Biomembranes最新文献

{"title":"Different lateral packing stress in acyl chains alters KcsA orientation and structure in lipid membranes","authors":"Eri Saki H. Hayakawa ,&nbsp;Misuzu Ueki ,&nbsp;Elmukhtar Alhatmi ,&nbsp;Shigetoshi Oiki ,&nbsp;Fuyuki Tokumasu ,&nbsp;Drake C. Mitchell ,&nbsp;Masayuki Iwamoto","doi":"10.1016/j.bbamem.2024.184338","DOIUrl":"10.1016/j.bbamem.2024.184338","url":null,"abstract":"<div><p>The molecular structures of the various intrinsic lipids in membranes regulate lipid-protein interactions. These different lipid structures with unique volumes produce different lipid molecular packing stresses/lateral stresses in lipid membranes. Most studies examining lipid packing effects have used phosphatidylcholine and phosphatidylethanolamine (PE), which are the main phospholipids of eukaryotic cell membranes. In contrast, Gram-negative or Gram-positive bacterial membranes are composed primarily of phosphatidylglycerol (PG) and PE, and the physical and thermodynamic properties of each acyl chain in PG at the molecular level remain unresolved. In this study, we used 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phospho-(1′-rac-glycerol) (POPG, 16:0–18:1 PG) and 1-palmitoyl-2-arachidonoyl-<em>sn</em>-glycero-3-phospho-(1′-rac-glycerol) (PAPG, 16:0–20:4 PG) to prepare lipid bilayers (liposome) with the rod-type fluorescence probe DPH. We measured the lipid packing conditions by determining the rotational freedom of DPH in POPG or PAPG bilayers. Furthermore, we investigated the effect of different monoacyl chains on a K⁺ channel (KcsA) structure when embedded in POPG or PAPG membranes. The results revealed that differences in the number of double bonds and carbon chain length in the monoacyl chain at <em>sn</em>-2 affected the physicochemical properties of the membrane and the structure and orientation of KcsA.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 6","pages":"Article 184338"},"PeriodicalIF":3.4,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flow-based bioconjugation of coumarin phosphatidylethanolamine probes: Optimised synthesis and membrane molecular dynamics studies","authors":"Pedro A.M.M. Varandas ,&nbsp;Ricardo Belinha ,&nbsp;Alexander J.A. Cobb ,&nbsp;João P. Prates Ramalho ,&nbsp;Marcela A. Segundo ,&nbsp;Luís M.S. Loura ,&nbsp;Eduarda M.P. Silva","doi":"10.1016/j.bbamem.2024.184335","DOIUrl":"10.1016/j.bbamem.2024.184335","url":null,"abstract":"<div><p>A series of phosphatidylethanolamine fluorescent probes head-labelled with 3-carboxycoumarin was prepared by an improved bioconjugation approach through continuous flow synthesis. The established procedure, supported by a design of experiment (DoE) set-up, resulted in a significant reduction in the reaction time compared to the conventional batch method, in addition to a minor yield increase. The characterization of these probes was enhanced by an in-depth molecular dynamics (MD) study of the behaviour of a representative probe of this family, 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphoethanolamine labelled with 3-carboxycoumarin (POPE-COUM), in bilayers of 1-palmitoyl-2-oleoyl-<em>sn</em>-glycero-3-phosphocholine (POPC)/1-stearoyl-2-linoleoyl-<em>sn</em>-glycero-3-phosphocholine (SLPC) 2:1, mimicking the composition of the egg yolk lecithin membranes recently used experimentally by our group to study POPE-COUM as a biomarker of the oxidation state and integrity of large unilamellar vesicles (LUVs). The MD simulations revealed that the coumarin group is oriented towards the bilayer interior, leading to a relatively internal location, in agreement with what is observed in the nitrobenzoxadiazole fluorophore of commercial head-labelled NBD-PE probes. This behaviour is consistent with the previously stated hypothesis that POPE-COUM is entirely located within the LUVs structure. Hence, the delay on the oxidation of the probe in the oxygen radical absorbance capacity (ORAC) assays performed is related with the inaccessibility of the probe until alteration of the LUV structure occurs. Furthermore, our simulations show that POPE-COUM exerts very little global and local perturbation on the host bilayer, as evaluated by key properties of the unlabelled lipids. Together, our findings establish PE-COUM as suitable fluorescent lipid analogue probes.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 7","pages":"Article 184335"},"PeriodicalIF":3.4,"publicationDate":"2024-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S000527362400066X/pdfft?md5=07714a0a3090784aa4fc7033fdd2c942&pid=1-s2.0-S000527362400066X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141065369","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}

{"title":"Development of protease resistant and non-cytotoxic Jelleine analogs with enhanced broad spectrum antimicrobial efficacy","authors":"Tanumoy Sarkar ,&nbsp;S.R. Vignesh ,&nbsp;Tanya Sehgal ,&nbsp;K.R. Ronima ,&nbsp;Rajkumar P. Thummer ,&nbsp;Priyadarshi Satpati ,&nbsp;Sunanda Chatterjee","doi":"10.1016/j.bbamem.2024.184336","DOIUrl":"10.1016/j.bbamem.2024.184336","url":null,"abstract":"<div><p>Short systemic half- life of Antimicrobial Peptides (AMP) is one of the major bottlenecks that limits their successful commercialization as therapeutics. In this work, we have designed analogs of the natural AMP Jelleine, obtained from royal jelly of <em>apis mellifera</em>. Among the designed peptides, <strong>J3</strong> and <strong>J4</strong> were the most potent with broad spectrum activities against a varied class of ESKAPE pathogens and fungus <em>C. albicans</em>. All the developed peptides were more effective against Gram-negative bacteria in comparison to the Gram-positive pathogens, and were especially effective against <em>P. aeruginosa</em> and <em>C. albicans.</em> <strong>J3</strong> and <strong>J4</strong> were completely trypsin resistant and serum stable, while retaining the non-cytotoxicity of the parent Jelleine, <strong>Jc</strong>. The designed peptides were membranolytic in their mode of action. CD and MD simulations in the presence of bilayers, established that <strong>J3</strong> and <strong>J4</strong> were non-structured even upon membrane binding and suggested that biological properties of the AMPs were innocent of any specific secondary structural requirements. Enhancement of charge to increase the antimicrobial potency, controlling the hydrophobic-hydrophilic balance to maintain non-cytotoxicity and induction of unnatural amino acid residues to impart protease resistance, remains some of the fundamental principles in the design of more effective antimicrobial therapeutics of the future, which may help combat the quickly rising menace of antimicrobial resistance in the microbes.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 6","pages":"Article 184336"},"PeriodicalIF":3.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141039424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G protein β subunits regulate Cav3.3 T-type channel activity and current kinetics via interaction with the Cav3.3 C-terminus","authors":"Sua Jeong ,&nbsp;Bo-Young Lee ,&nbsp;Jeong Seop Rhee ,&nbsp;Jung-Ha Lee","doi":"10.1016/j.bbamem.2024.184337","DOIUrl":"10.1016/j.bbamem.2024.184337","url":null,"abstract":"<div><p>Ca²⁺ influx through Ca_v3.3 T-type channel plays crucial roles in neuronal excitability and is subject to regulation by various signaling molecules. However, our understanding of the partners of Ca_v3.3 and the related regulatory pathways remains largely limited. To address this quest, we employed the rat Ca_v3.3 C-terminus as bait in yeast-two-hybrid screenings of a cDNA library, identifying rat Gβ₂ as an interaction partner. Subsequent assays revealed that the interaction of Gβ₂ subunit was specific to the Ca_v3.3 C-terminus. Through systematic dissection of the C-terminus, we pinpointed a 22 amino acid sequence (amino acids 1789–1810) as the Gβ₂ interaction site. Coexpression studies of rat Ca_v3.3 with various Gβγ compositions were conducted in HEK-293 cells. Patch clamp recordings revealed that coexpression of Gβ₂γ₂ reduced Ca_v3.3 current density and accelerated inactivation kinetics. Interestingly, the effects were not unique to Gβ₂γ_2, but were mimicked by Gβ₂ alone as well as other Gβγ dimers, with similar potencies. Deletion of the Gβ₂ interaction site abolished the effects of Gβ₂γ₂. Importantly, these Gβ₂ effects were reproduced in human Ca_v3.3. Overall, our findings provide evidence that Gβ(γ) complexes inhibit Ca_v3.3 channel activity and accelerate the inactivation kinetics through the Gβ interaction with the Ca_v3.3 C-terminus.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 6","pages":"Article 184337"},"PeriodicalIF":3.4,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141028948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cholesterol drives enantiospecific effects of ibuprofen in biomimetic membranes","authors":"Alexa Guglielmelli ,&nbsp;Caterina M. Tone ,&nbsp;Eleonora Ragozzino ,&nbsp;Federica Ciuchi ,&nbsp;Rosa Bartucci","doi":"10.1016/j.bbamem.2024.184334","DOIUrl":"10.1016/j.bbamem.2024.184334","url":null,"abstract":"<div><p>The interaction between chiral drugs and biomimetic membranes is of interest in biophysical research and biotechnological applications. There is a belief that the membrane composition, particularly the presence of cholesterol, could play a pivotal role in determining enantiospecific effects of pharmaceuticals. Our study explores this topic focusing on the interaction of ibuprofen enantiomers (S- and R-IBP) with cholesterol-containing model membranes. The effects of S- and R-IBP at 20 mol% on bilayer mixtures of dipalmitoylphosphatidylcholine (DPPC) with 0, 10, 20 and 50 mol% cholesterol were investigated using circular dichroism and spin-label electron spin resonance. Morphological changes due to IBP enantiomers were studied with atomic force microscopy on supported cholesterol-containing DPPC monolayers. The results reveal that IBP isoforms significantly and equally interact with pure DPPC lipid assemblies. Cholesterol content, besides modifying the structure and the morphology of the membranes, triggers the drug enantioselectivity at 10 and 20 mol%, with the enantiomers differently adsorbing on membranes and perturbing them. The spectroscopic and the microscopic data indicate that IBP stereospecificity is markedly reduced at equimolar content of Chol mixed with DPPC. This study provides new insights into the role of cholesterol in modulating enantiospecific effects of IBP in lipid membranes.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184334"},"PeriodicalIF":3.4,"publicationDate":"2024-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0005273624000658/pdfft?md5=331cc2e8f80638d37642e05ad0b8f544&pid=1-s2.0-S0005273624000658-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140921014","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}

{"title":"Effects induced by η6-p-cymene ruthenium(II) complexes on Langmuir monolayers mimicking cancer and healthy cell membranes do not correlate with their toxicity","authors":"Ellen C. Wrobel ,&nbsp;Ivelise Dimbarre Lao Guimarães ,&nbsp;Karen Wohnrath ,&nbsp;Osvaldo N. Oliveira Jr","doi":"10.1016/j.bbamem.2024.184332","DOIUrl":"10.1016/j.bbamem.2024.184332","url":null,"abstract":"<div><p>The mechanism of chemotherapeutic action of Ru-based drugs involves plasma membrane disruption and valuable insights into this process may be gained using cell membrane models. The interactions of a series of cytotoxic η⁶-<em>p</em>-cymene ruthenium(II) complexes, [Ru(η⁶-<em>p</em>-cymene)P(3,5-C(CH₃)₃-C₆H₃)₃Cl₂] <strong>(1)</strong>, [Ru(η⁶-<em>p</em>-cymene)P(3,5-CH₃-C₆H₃)₃Cl₂] <strong>(2)</strong>, [Ru(η⁶-<em>p</em>-cymene)P(4-CH₃O-3,5-CH₃-C₆H₂)₃Cl₂] <strong>(3)</strong>, and [Ru(η⁶-<em>p</em>-cymene)P(4-CH₃O-C₆H₄)₃Cl₂] <strong>(4)</strong>, were examined using Langmuir monolayers as simplified healthy and cancerous outer leaflet plasma membrane models. The cancerous membrane (CM1 and CM2) models contained either 40 % 1,2- dipalmitoyl-<em>sn</em>-glycero-3-phosphocholine (DPPC) or 1,2-dioleoyl-<em>sn</em>-glycero-3-phosphocholine (DOPC), 30 % cholesterol (Chol), 20 % 1,2-dipalmitoyl-<em>sn</em>-glycero-3-phosphoethanolamine (DPPE), and 10 % 1,2-dipalmitoyl-<em>sn</em>-glycero-3-phospho-<em><span>l</span></em>-serine (DPPS). Meanwhile, the healthy membrane (HM1 and HM2) models were composed of 60 % DPPC or DOPC, 30 % Chol and 10 % DPPE. The complexes affected surface pressure isotherms and decreased compressional moduli of cancerous and healthy membrane models, interacting with the monolayers headgroup and tails according to data from polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS). However, the effects did not correlate with the toxicity of the complexes to cancerous and healthy cells. Multidimensional projection technique showed that the complex <strong>(1)</strong> induced significant changes in the CM1 and HM1 monolayers, though it had the lowest cytotoxicity against cancer cells and is not toxic to healthy cells. Moreover, the most toxic complexes <strong>(2)</strong> and <strong>(4)</strong> were those that least affected CM2 and HM2 monolayers. The findings here support that the ruthenium complexes interact with lipids and cholesterol in cell membrane models, and their cytotoxic activities involve a multifaceted mode of action beyond membrane disruption.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184332"},"PeriodicalIF":3.4,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916013","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helical reorganization in the context of membrane protein folding: Insights from simulations with bacteriorhodopsin (BR) fragments","authors":"Hindol Chatterjee ,&nbsp;Anshuman J. Mahapatra ,&nbsp;Martin Zacharias ,&nbsp;Neelanjana Sengupta","doi":"10.1016/j.bbamem.2024.184333","DOIUrl":"10.1016/j.bbamem.2024.184333","url":null,"abstract":"<div><p>Membrane protein folding is distinct from folding of soluble proteins. Conformational acquisition in major membrane protein subclasses can be delineated into insertion and folding processes. An exception to the “two stage” folding, later developed to “three stage” folding, is observed within the last two helices in bacteriorhodopsin (BR), a system that serves as a model membrane protein. We employ a reductionist approach to understand interplay of molecular factors underlying the apparent defiance. Leveraging available solution NMR structures, we construct, sample in silico, and analyze partially (PIn) and fully inserted (FIn) BR membrane states. The membrane lateral C-terminal helix (CH) in PIn is markedly prone to transient structural distortions over microsecond timescales; a disorder prone region (DPR) is thereby identified. While clear transmembrane propensities are not acquired, the distortions induce alterations in local membrane curvature and area per lipid. Importantly, energetic decompositions reveal that overall, the N-terminal helix (NH) is thermodynamically more stable in the PIn. Higher overall stability of the FIn arises from favorable interactions between the NH and the CH. Our results establish lack of spontaneous transition of the PIn to the FIn, and attributes their partitioning to barriers that exceed those accessible with thermal fluctuations. This work paves the way for further detailed studies aimed at determining the thermo-kinetic roles of the initial five helices, or complementary external factors, in complete helical folding and insertion in BR. We comment that complementing such efforts with the growing field of machine learning assisted energy landscape searches may offer unprecedented insights.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184333"},"PeriodicalIF":3.4,"publicationDate":"2024-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140916020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exogenous polyserine fibrils change membrane properties of phosphatidylcholine-liposome and red blood cells","authors":"Yutaro Iizuka ,&nbsp;Akiko Katano-Toki ,&nbsp;Fumio Hayashi ,&nbsp;Jun Fujioka ,&nbsp;Hiroshi Takahashi ,&nbsp;Kazuhiro Nakamura","doi":"10.1016/j.bbamem.2024.184331","DOIUrl":"10.1016/j.bbamem.2024.184331","url":null,"abstract":"<div><p>The causative genes for neurodegenerative polyglutamine (polyQ) diseases produce homopolymeric polyglutamine (polyQ), polyserine (polyS), polyalanine (polyA), polycysteine (polyC), and polyleucine (polyL) sequences by repeat-associated non-AUG (RAN) translation. The cytotoxicity of the intracellular polyQ and RAN products has been extensively investigated. However, little is known about the toxicity of the extracellular polyQ and RAN products on the membranes of viable cells. Because polyQ aggregates induce a deflated morphology of a model membrane, we hypothesized that extracellular polyQ and RAN products might affect the membrane properties of viable cells. In this study, we demonstrated that exogenous polyS fibrils but not polyS or polyQ non-fibril aggregates altered the thermal phase transition behavior of a model membrane composed of a phosphatidylcholine bilayer using differential scanning calorimetry. PolyS fibrils induced morphological changes in viable red blood cells (RBCs). However, both polyS and polyQ non-fibril aggregates had no effects on RBCs. These results highlight the possibility that extracellular fibrils generated from RAN products may alter the properties of neuronal cell membranes, which may contribute to changes in the brain pathology.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184331"},"PeriodicalIF":3.4,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140891372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Notable enhancement of Amphotericin B channel activity by applied pressures in the range of MS channel activation","authors":"Tammy Haro-Reyes,&nbsp;Iván Ortega-Blake","doi":"10.1016/j.bbamem.2024.184326","DOIUrl":"https://doi.org/10.1016/j.bbamem.2024.184326","url":null,"abstract":"<div><p>The mechanism of Amphotericin B at the membrane is still subject of debate, with the prevailing hypothesis being the formation of pores. The activity of these pores is influenced by various factors. Recently aggregation in solution and insertion in the membrane had been highlighted as crucial for action of the drug</p><p>Here we investigated the effect of applied pressure on the activity of Amphotericin B. Our findings demonstrate that applied pressure of 50 mmHg is sufficient to enhance the activity.</p><p>We interpreted the results as supporting the idea that pressure fractures the membrane and promotes the insertion of the polyene</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184326"},"PeriodicalIF":3.4,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The molecular arrangement of ceramides in the unit cell of the long periodicity phase of stratum corneum models shows a high adaptability to different ceramide head group structures","authors":"Andreea Nădăban ,&nbsp;Gerrit S. Gooris ,&nbsp;Charlotte M. Beddoes ,&nbsp;Robert M. Dalgliesh ,&nbsp;Marc Malfois ,&nbsp;Bruno Demé ,&nbsp;Joke A. Bouwstra","doi":"10.1016/j.bbamem.2024.184324","DOIUrl":"https://doi.org/10.1016/j.bbamem.2024.184324","url":null,"abstract":"<div><p>The stratum corneum (SC) lipid matrix, composed primarily of ceramides (CERs), cholesterol and free fatty acids (FFA), has an important role for the skin barrier function. The presence of the long periodicity phase (LPP), a unique lamellar phase, is characteristic for the SC. Insight into the lipid molecular arrangement within the LPP unit cell is imperative for understanding the relationship between the lipid subclasses and the skin barrier function. In this study, the impact of the CER head group structure on the lipid arrangement and barrier functionality was investigated using lipid models forming the LPP. The results demonstrate that the positions of CER <em>N</em>-(tetracosanoyl)-sphingosine (CER NS) and CER <em>N</em>-(tetracosanoyl)-phytosphingosine (CER NP), two essentials CER subclasses, are not influenced by the addition of another CER subclass (<em>N</em>-(tetracosanoyl)-dihydrosphingosine (CER NdS), <em>N</em>-(2R-hydroxy-tetracosanoyl)-sphingosine (CER AS) or D-(2R-hydroxy-tetracosanoyl)-phytosphingosine (CER AP)). However, differences are observed in the lipid organization and the hydrogen bonding network of the three different models. A similar localization of CER NP and CER NS is also observed in a more complex lipid model, with the CER subclass composition mimicking that of human SC. These studies show the adaptability and insensitivity of the LPP unit cell structure to changes in the lipid head group structures of the CER subclasses.</p></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1866 5","pages":"Article 184324"},"PeriodicalIF":3.4,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0005273624000555/pdfft?md5=413b5cd0ac026b81be015cbcfba400f5&pid=1-s2.0-S0005273624000555-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140823970","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}