Chemistry and Physics of Lipids最新文献

{"title":"The influence of amphiphilic carbosilane dendrons on lipid model membranes","authors":"Dominika Wrobel ,&nbsp;Antonin Edr ,&nbsp;Eliska Zemanova ,&nbsp;Tomáš Strašák ,&nbsp;Alena Semeradtova ,&nbsp;Jan Maly","doi":"10.1016/j.chemphyslip.2023.105314","DOIUrl":"10.1016/j.chemphyslip.2023.105314","url":null,"abstract":"<div><p><span>Amphiphilic dendrons represent a relatively novel class of molecules which may show many unique properties suitable for applications in a field of molecular biology and </span>nanomedicine<span><span>. They were frequently studied as platforms suitable for drug delivery systems as were, e.g. polymersomes or hybrid lipid-polymer nanoparticles. Recently, natural extracellular </span>lipid vesicles<span> (EVs), called exosomes (EXs), were shown to be a promising candidate in drug delivery applications. Formation of hybrid exosome-dendron nanovesicles could bring benefits in their simple conjugation with selective targeting moieties. Unfortunately, the complex architecture of biological membranes, EXs included, makes obstacles in elucidating the important parameters and mechanisms of interaction with the artificial amphiphilic structures.</span></span></p><p><span>The aim of the presented work was to study the interaction of two types of amphiphilic carbosilane dendritic structures (denoted as DDN-1 and DDN-2) suitable for further modification with streptavidin<span> (DDN-1) or using click-chemistry approach (DDN-2), with selected neutral and negatively charged lipid<span> model membranes<span>, partially mimicking the basic properties of natural EXs biomembranes. To meet the goal, a number of biophysical methods<span> were used for determination of the degree and mechanisms of the interaction. The results showed that the strength of interactions of amphiphilic dendrons with liposomes was related with surface charge of liposomes. Several steps of interactions were disclosed. The initialization step was mainly coupled with amphiphilic dendrons - liposomes surface interaction resulting in destabilization of large self-assembled amphiphilic dendrons structures. Such destabilization was more significant with liposomes of higher negative charge. With increasing concentration of amphiphilic dendrons in a solution the interactions were taking place also in the hydrophobic part of bilayer. Further increase of nanoparticle concentration resulted in a gradual dendritic cluster formation in a </span></span></span></span></span>lipid bilayer structure.</p><p>Due to high affinity of amphiphilic dendrons to model lipid bilayers the conclusion can be drawn that they represent promising platforms also for decoration of exosomes or other kinds of natural lipid vehicles. Such organized hybrid dendron-lipid biomembranes may be advantageous for their subsequent post-functionalization with small molecules, large biomacromolecules or polymers suitable for targeted drug-delivery or theranostic applications.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"255 ","pages":"Article 105314"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205000","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":"Solubilization of biomimetic lipid mixtures by some commonly used non-ionic detergents","authors":"Amanda C. Caritá ,&nbsp;Rafaela R.M. Cavalcanti,&nbsp;Mariana S.S. Oliveira,&nbsp;Karin A. Riske","doi":"10.1016/j.chemphyslip.2023.105327","DOIUrl":"10.1016/j.chemphyslip.2023.105327","url":null,"abstract":"<div><p><span><span>Detergents are amphiphilic molecules often used to solubilize biological membranes<span> and separate their components. Here we investigate the solubilization of </span></span>lipid vesicles by the commonly used non-ionic detergents polyoxyethylene (20) oleyl ether (Brij 98), n-octyl-β-</span><span>D</span><span><span>-glucoside (OG), and n-dodecyl β-D maltoside<span><span> (DDM) and compare the results with the standard detergent Triton X-100 (TX-100). The vesicles were composed of palmitoyl oleoyl phosphatidylcholine<span> (POPC) or of a biomimetic<span> ternary mixture of POPC, egg </span></span></span>sphingomyelin<span> (SM) and cholesterol (2:1:2 molar ratio). To follow the solubilization profile of large unilamellar vesicles (LUVs), 90° light scattering measurements were done along the titration of LUVs with the detergents. Then, giant unilamellar vesicles (GUVs) were observed with </span></span></span>optical microscopy<span> during exposure to the detergents, to allow direct visualization of the solubilization process. Isothermal titration calorimetry<span> (ITC) was used to assess the binding constant<span> of the detergents in POPC bilayers<span>. The results show that the incorporation of TX-100, Brij 98 and, to a lesser extent, OG in the pure POPC liposomes leads to an increase in the vesicle area, which indicates their ability to redistribute between the two leaflets of the membrane in a short scale of time. On the other hand, DDM incorporates mainly in the external leaflet causing an increase in vesicle curvature/tension leading ultimately to vesicle burst. Only TX-100 and OG were able to completely solubilize the POPC vesicles, whereas the biomimetic ternary mixture was partially insoluble in all detergents tested. TX-100 and OG were able to incorporate in the bilayer of the ternary mixture and induce macroscopic phase separation of liquid-ordered (</span></span></span></span></span><em>Lo</em>) and liquid-disordered (<em>Ld</em><span>) domains, with selective solubilization of the latter. Combination of ITC data with turbidity results showed that TX-100 and OG can be incorporated up to almost 0.3 detergent/lipid, significantly more than Brij 98 and DDM. This fact seems to be directly related to their higher capacity to solubilize POPC membranes and their ability to induce macroscopic phase separation in the biomimetic lipid mixture.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"255 ","pages":"Article 105327"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9986853","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":"Transethosome: An ultra-deformable ethanolic vesicle for enhanced transdermal drug delivery","authors":"Alan Raj ,&nbsp;Kamal Dua ,&nbsp;Rajesh Sreedharan Nair ,&nbsp;C. Sarath Chandran ,&nbsp;Angel Treasa Alex","doi":"10.1016/j.chemphyslip.2023.105315","DOIUrl":"10.1016/j.chemphyslip.2023.105315","url":null,"abstract":"<div><p><span>Drug delivery through the skin improves solubility, bioavailability, and unwanted systemic side effects of the drug. The selection of a suitable carrier is a challenging process. The conventional lipid vesicles<span> have some limitations. They deliver the drug in the stratum corneum and have poor colloidal stability. Here comes the need for ultra-deformable lipid vesicles to provide the drug beyond the stratum corneum. Transethosomes are novel ultra-deformable vesicles that can deliver drugs into deeper tissues. The composition of transethosomes includes </span></span>phospholipid, ethanol and surfactants. Each ingredient has a pivotal role in the properties of the carrier. This review covers the design, preparation method, characterisation, and characteristics of the novel vesicle. Also, we cover the impact of surfactants on vesicular properties and the skin permeation behaviour of novel vesicles.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"255 ","pages":"Article 105315"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10204998","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":"Membrane lipid composition of Carnobacterium maltaromaticum CNCM I-3298, a highly cryoresistant lactic bacterium","authors":"HP. Ta ,&nbsp;C. Clarisse ,&nbsp;E. Maes ,&nbsp;N. Yamakawa ,&nbsp;Y. Guérardel ,&nbsp;F. Krzewinski ,&nbsp;W. Zarzycka ,&nbsp;D. Touboul ,&nbsp;A. Girardeau ,&nbsp;F. Fonseca ,&nbsp;A. Kermarrec ,&nbsp;M. Viau ,&nbsp;A. Riaublanc ,&nbsp;MH. Ropers","doi":"10.1016/j.chemphyslip.2023.105326","DOIUrl":"10.1016/j.chemphyslip.2023.105326","url":null,"abstract":"<div><p><span>The growing consumption of fermented products has led to an increasing demand for lactic acid bacteria (LAB), especially for LAB tolerant to freezing/thawing conditions. </span><span><em>Carnobacterium</em><em> maltaromaticum</em></span><span><span> is a psychrotrophic and freeze-thawing resistant lactic acid bacterium. The membrane is the primary site of damage during the cryo-preservation process and requires modulation to improve cryoresistance. However, knowledge about the membrane structure of this LAB genus is limited. We presented here the first study of the membrane </span>lipid<span> composition of </span></span><em>C. maltaromaticum</em><span><span> CNCM I-3298 including the polar heads and the fatty acid compositions of each lipid family (neutral lipids, glycolipids, phospholipids). The strain CNCM I-3298 is principally composed of glycolipids (32%) and </span>phospholipids<span> (55%). About 95% of glycolipids are dihexaosyldiglycerides while less than 5% are monohexaosyldiglycerides. The disaccharide chain of dihexaosyldiglycerides is composed of α-Gal(1−2)-α-Glc chain, evidenced for the first time in a LAB strain other than </span></span><span><em>Lactobacillus</em></span><span> strains. Phosphatidylglycerol is the main phospholipid (94%). All polar lipids are exceptionally rich in C18:1 (from 70% to 80%). Regarding the fatty acid composition, </span><em>C. maltaromaticum</em> CNCM I-3298 is an atypical bacterium within the genus <em>Carnobacterium</em> due to its high C18:1 proportion but resemble the other <em>Carnobacterium</em><span> strains as they mostly do not contain cyclic fatty acids.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"255 ","pages":"Article 105326"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10205021","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":"Recent advances in regulating lipid metabolism to prevent coronary heart disease","authors":"Jingchun Du ,&nbsp;Wei Wu ,&nbsp;Boran Zhu ,&nbsp;Weiwei Tao ,&nbsp;Lina Liu ,&nbsp;Xiaolan Cheng ,&nbsp;Min Zhao ,&nbsp;Jibiao Wu ,&nbsp;Yunlun Li ,&nbsp;Ke Pei","doi":"10.1016/j.chemphyslip.2023.105325","DOIUrl":"10.1016/j.chemphyslip.2023.105325","url":null,"abstract":"<div><p><span><span>The pathogenesis of coronary heart disease is a highly complex process, with lipid metabolism disorders being closely linked to its development. Therefore, this paper analyzes the various factors that influence lipid metabolism, including obesity, genes, </span>intestinal microflora<span>, and ferroptosis, through a comprehensive review of basic and clinical studies. Additionally, this paper delves deeply into the pathways and patterns of coronary heart disease. Based on these findings, it proposes various intervention pathways and therapeutic methods, such as the regulation of </span></span>lipoprotein<span> enzymes, lipid metabolites, and lipoprotein regulatory factors, as well as the modulation of intestinal microflora and the inhibition of ferroptosis. Ultimately, this paper aims to offer new ideas for the prevention and treatment of coronary heart disease.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"255 ","pages":"Article 105325"},"PeriodicalIF":3.4,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10502958","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":"Characterization of conformational states of POPC and DPPCd62 in POPC/DPPCd62/cholesterol mixtures using Raman spectroscopy","authors":"Yu.V. Zaytseva,&nbsp;I.V. Zaytseva,&nbsp;N.V. Surovtsev","doi":"10.1016/j.chemphyslip.2023.105337","DOIUrl":"https://doi.org/10.1016/j.chemphyslip.2023.105337","url":null,"abstract":"<div><p><span>Conformational states of phospholipid<span> chains in ternary mixtures of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), deuterated 1,2-dipalmitoyl-d62-sn-glycero-3-phosphocholine (DPPC</span></span>_d62<span>), and cholesterol (Chol) were studied by Raman spectroscopy<span>. Parameters of Raman peaks sensitive to conformational order have been used to determine chain order for mixtures over a wide range of compositions. A ternary diagram of fractions of phospholipid chains in conformationally ordered and disordered states has been constructed. It was found that the addition of POPC and cholesterol increases the fraction of DPPC chains in disordered conformations. The so-called liquid-ordered phase includes DPPC molecules in both ordered and disordered states in comparable proportions. It was found that POPC chains are partially ordered in mixtures with DPPC and cholesterol, in contrast to the case of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC). This maybe the underlying reason why ternary mixtures with POPC have different miscibility behavior compared to DOPC.</span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"256 ","pages":"Article 105337"},"PeriodicalIF":3.4,"publicationDate":"2023-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"3273686","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":"Effect of cholesterol on the ion-membrane interaction: Zeta potential and dynamic light scattering study","authors":"Kalyan Kumar Banerjee,&nbsp;Pabitra Maity,&nbsp;Surajit Das,&nbsp;Sanat Karmakar","doi":"10.1016/j.chemphyslip.2023.105307","DOIUrl":"10.1016/j.chemphyslip.2023.105307","url":null,"abstract":"<div><p>Cholesterol in a bio-membrane plays a significant role in many cellular event and is known to regulate the functional activity of protein and ion channel. In this study we report a significant effect of cholesterol on the ion-membrane interaction. We prepare large unilamellar vesicles<span><span><span>, composed of zwitterionic lipid </span>DOPC and anionic lipid DOPG with different cholesterol concentration. Electrostatics of anionic membranes containing cholesterol in the presence of </span>NaCl<span><span> has systematically been explored using dynamic light scattering and </span>zeta potential<span>. Negative zeta potential of the membrane decreases its negative value with increasing ion concentration for all cholesterol concentrations. However, zeta potential itself decreases with increasing cholesterol content even in the absence of monovalent ions. Electrostatic behaviour of the membrane is determined from well-known Gouy Chapmann model. Negative surface charge density of the membrane decreases with increasing cholesterol content. Binding constant, estimated from the electrostatic double layer theory, is found to increase significantly in the presence of cholesterol. Comparison of electrostatic parameters of the membrane in the presence and absence of cholesterol suggests that cholesterol significantly alter the electrostatic behaviour of the membrane.</span></span></span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"254 ","pages":"Article 105307"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690615","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":"Porcine spermadhesin AQN-3 binds to negatively charged phospholipids","authors":"Karin Müller ,&nbsp;Peter Müller ,&nbsp;Fan Lui ,&nbsp;Pascal D. Kroh ,&nbsp;Beate C. Braun","doi":"10.1016/j.chemphyslip.2023.105306","DOIUrl":"10.1016/j.chemphyslip.2023.105306","url":null,"abstract":"<div><p><span><span><span>The spermadhesin AQN-3 is a major component of porcine seminal plasma. While various studies suggest that this protein binds to boar sperm cells, its attachment to the cells is poorly understood. Therefore, the capacity of AQN-3 to interact with lipids was investigated. For that purpose, AQN-3 was recombinantly expressed in </span>E. coli and purified via the included His-tag. Characterizing the </span>quaternary structure by size exclusion chromatography revealed that recombinant AQN-3 (recAQN-3) is largely present as multimer and/or aggregate. To determine the lipid specificity of recAQN-3, a lipid stripe method and a multilamellar vesicle (MLV)-based binding assay were used. Both assays show that recAQN-3 selectively interacts with negatively charged lipids, like </span>phosphatidic acid<span><span><span><span>, phosphatidylinositol<span> phosphates, and cardiolipin<span>. No interaction was observed with phosphatidylcholine, </span></span></span>sphingomyelin, </span>phosphatidylethanolamine<span>, or cholesterol. The affinity to negatively charged lipids can be explained by electrostatic interactions<span> because binding is partly reversed under high-salt condition. However, more factors have to be assumed like hydrogen bonds<span> and/or hydrophobic forces because the majority of bound molecules was not released by high salt. To confirm the observed binding behavior for the native protein, porcine seminal plasma was incubated with MLVs comprising phosphatidic acid or phosphatidyl-4,5-bisphosphate. Attached proteins were isolated, digested, and analyzed by mass spectrometry. Native AQN-3 was detected in all samples analyzed and was – besides AWN – the most abundant protein. It remains to be investigated whether AQN-3, together with other sperm associated seminal </span></span></span></span>plasma proteins, acts as decapacitation factor by targeting negative lipids with signaling or other functional roles in fertilization.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"254 ","pages":"Article 105306"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9690610","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":"Comparative analysis of intercellular lipid organization and composition between psoriatic and healthy stratum corneum","authors":"Tomonobu Uchino ,&nbsp;Daichi Kamiya ,&nbsp;Hiroaki Yagi ,&nbsp;Hiyori Fujino-Shimaya ,&nbsp;Ichiro Hatta ,&nbsp;Shun Fujimori ,&nbsp;Yasunori Miyazaki ,&nbsp;Yukako Kirishita ,&nbsp;Yuko Sano ,&nbsp;Hajime Mizuno ,&nbsp;Kenichiro Todoroki ,&nbsp;Yoshiyuki Kagawa","doi":"10.1016/j.chemphyslip.2023.105305","DOIUrl":"10.1016/j.chemphyslip.2023.105305","url":null,"abstract":"<div><p><span><span><span>The lipid composition and organization of the stratum corneum (SC) in patients with psoriasis and healthy subjects were compared using X-ray diffraction, Fourier-transform infrared spectroscopy (FT-IR), and ultraperformance </span>liquid chromatography, combined with time-of-flight mass spectrometry (UPLC-TOFMS). In healthy SC (HSC), SC </span>lipids<span> formed two lamellar phases (long and short periodicity phases). Hexagonal and orthorhombic hydrocarbon-chain packing were observed in the lateral lipid organization at 30 °C via X-ray diffraction. In HSC, the lamellar phases and the hydrocarbon-chain packing organizations changed with elevated temperatures and finally disappeared. In these behaviors, the high-temperature hexagonal hydrocarbon-chain packing organization, which appeared above the orthorhombic hydrocarbon-chain packing organization, transformed to the liquid phase at about 90 °C in HSC. In psoriatic SC (PSC), hexagonal hydrocarbon-chain packing organization disappeared at about 65 °C with elevated temperatures. No high-temperature hexagonal hydrocarbon-chain packing organization were observed in PSC during heating process. Disorder of the hydrocarbon-chain packing of SC lipids was observed in PSC via FT-IR. In UPLC-TOFMS, free fatty acid (FFA) and </span></span>ceramide<span> (CER) compositions differed between patients with PSC and HSC. Specifically, the levels of ultra-long chain fatty acids containing CER and phytosphingosine-containing CER were decreased, while those of sphingosine and dihydrosphingosine-containing CER and unsaturated FFA were increased in PSC. Furthermore, FFA and CER carbon chain lengths decreased in patients with PSC. These results suggest that the alteration of SC lipid composition and the reduction of carbon chain lengths in PSC lowered the structural transformation temperature, thereby reducing barrier function.</span></p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"254 ","pages":"Article 105305"},"PeriodicalIF":3.4,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9682317","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":"Labyrinthopeptin A2 disrupts raft domains","authors":"José Villalaín","doi":"10.1016/j.chemphyslip.2023.105303","DOIUrl":"10.1016/j.chemphyslip.2023.105303","url":null,"abstract":"<div><p>Labyrinthopeptins constitute a class of ribosomal synthesized peptides belonging to the type III family of lantibiotics. They exist in different variants and display broad antiviral activities as well as show antiallodynic activity. Although their mechanism of action is not understood, it has been described that Labyrinthopeptins interact with membrane phospholipids modulating its biophysical properties and point out to membrane destabilization as its main point of action. We have used all-atom molecular dynamics to study the location of labyrinthopeptin A2 in a complex membrane as well as the existence of specific interactions with membrane lipids. Our results indicate that labyrinthopeptin A2, maintaining its globular structure, tends to be placed at the membrane interface, mainly between the phosphate atoms of the phospholipids and the oxygen atom of cholesterol modulating the biophysical properties of the membrane lipids. Outstandingly, we have found that labyrinthopeptin A2 tends to be preferentially surrounded by sphingomyelin while excluding cholesterol. The bioactive properties of labyrinthopeptin A2 could be attributed to the specific disorganization of raft domains in the membrane and the concomitant disruption of the overall membrane organization. These results support the improvement of Labyrinthopeptins as therapeutic molecules, opening up new opportunities for future medical advances.</p></div>","PeriodicalId":275,"journal":{"name":"Chemistry and Physics of Lipids","volume":"253 ","pages":"Article 105303"},"PeriodicalIF":3.4,"publicationDate":"2023-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0009308423000257/pdfft?md5=06609d33be348fc01c786a93a4b53f30&pid=1-s2.0-S0009308423000257-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9629451","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}