Biochimica et biophysica acta. Biomembranes最新文献_第2页

Reverse micelles produce hydroxyapatite nanoparticles as more efficient gene delivery carriers than regular micelles 反向胶束产生的羟基磷灰石纳米颗粒作为比常规胶束更有效的基因传递载体。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-22 DOI: 10.1016/j.bbamem.2026.184506

Vuk Uskoković

{"title":"Reverse micelles produce hydroxyapatite nanoparticles as more efficient gene delivery carriers than regular micelles","authors":"Vuk Uskoković","doi":"10.1016/j.bbamem.2026.184506","DOIUrl":"10.1016/j.bbamem.2026.184506","url":null,"abstract":"<div><div>Hydroxyapatite (HAp) is an effective inorganic gene delivery carrier due to its ability to transport genetic cargo across cell membranes, protect it from proteolysis, and enable escape from late endosomes via pH-controlled dissolution. However, its transfection efficiency remains lower than that of viral agents, prompting studies of hybrids with cationic molecules or phases to enhance the gene delivery performance. This study reports on the synthesis of HAp in regular and reverse micellar regions of a ternary microemulsion system composed of cetyltrimethylammonium bromide (CTAB), 1-hexanol and water. Spectroscopic characterization revealed that CTAB headgroups adopted more ordered supramolecular conformations in reverse micelles compared to regular ones. Similarly, water within reverse micelles exhibited more homogeneity and unexpected freedom, creating favorable entropic conditions for chemical reactions. CTAB showed strong electrostatic affinity for DNA and bound more effectively to HAp synthesized within the confined nanoscale environment of reverse micelles than to HAp produced in the aqueous continuum surrounding regular micelles. Also, reverse micelles produced narrowly dispersed, rod-shaped HAp nanoparticles, unlike the larger, macroporous particles formed in regular micelles. Both of these effects predisposed HAp from reverse micelles to exhibit a higher transfection efficiency in K7M2 osteosarcoma cells than its regular micelle counterpart. Despite these positive outcomes, HAp could only partially mitigate the cytotoxic effects of CTAB. Therefore, further exploration of advanced synthesis methods, biocompatible surfactants or strategies to preserve the synergy between HAp, CTAB and DNA while reducing CTAB toxicity is essential for enhancing the gene delivery performance of reverse micellar HAp.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184506"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146043557","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}

引用次数: 0

Effect of ice recrystallization inhibition on hydrogen bonding interactions and membrane leakage of liposomes 冰重结晶抑制对脂质体氢键相互作用和膜渗漏的影响。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bbamem.2026.184502

Dejia Liu , Harriëtte Oldenhof , Harald Sieme , Willem F. Wolkers

{"title":"Effect of ice recrystallization inhibition on hydrogen bonding interactions and membrane leakage of liposomes","authors":"Dejia Liu , Harriëtte Oldenhof , Harald Sieme , Willem F. Wolkers","doi":"10.1016/j.bbamem.2026.184502","DOIUrl":"10.1016/j.bbamem.2026.184502","url":null,"abstract":"<div><div>In this study, effects of ice recrystallization on membrane stability of liposomes were investigated using liposomes encapsulating a fluorescent dye. Membrane leakage was studied after freezing and storage at varying temperatures in solutions supplemented with polyvinyl alcohol (PVA), polyethylene glycol (PEG), dimethyl sulfoxide (DMSO) and combinations thereof. Leakage studies were corroborated with studies on ice crystal growth and hydrogen bonding interactions during holding at temperatures just below the ice melting temperature, i.e., at −10 °C. Cryomicroscopic observations confirmed that PVA exhibits ice recrystallization inhibition activity, whereas PEG did not. Both PVA and PEG reduced freezing-induced liposome leakage, alone and in combination with low DMSO concentrations. Temperature-scanning infrared spectroscopy (FTIR) combined with principal component analysis (PCA) was used as a novel approach to probe differences in hydrogen bonding interactions between frozen buffered saline (PBS) containing PVA and PEG. Score and loading plots show that symmetric hydrogen bonds are predominant with addition of PVA, and that the cluster of principal component data points remain compact during holding under ice recrystallization conditions. By contrast, PBS supplemented with PEG and PBS control solutions are characterized by weak hydrogen bonding interactions and more disperse clusters of principal component data points denoting rearrangements in hydrogen bonding interactions associated with ice crystal growth during holding. In conclusion, beneficial effects of adding PVA or PEG in cryopreservation solutions for liposomes are most evident under suboptimal cryopreservation conditions, e.g., during storage at elevated subzero temperatures, and when low concentrations of DMSO are used.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184502"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028343","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}

引用次数: 0

NMR structural analysis and peptidoglycan binding properties of the peptidoglycan associated lipoprotein (PAL) from Escherichia coli 大肠杆菌肽聚糖相关脂蛋白（PAL）的核磁共振结构分析及肽聚糖结合特性。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-20 DOI: 10.1016/j.bbamem.2026.184501

Ishrat M. Jalal , Hiroaki Ishida , Hans J. Vogel

{"title":"NMR structural analysis and peptidoglycan binding properties of the peptidoglycan associated lipoprotein (PAL) from Escherichia coli","authors":"Ishrat M. Jalal , Hiroaki Ishida , Hans J. Vogel","doi":"10.1016/j.bbamem.2026.184501","DOIUrl":"10.1016/j.bbamem.2026.184501","url":null,"abstract":"<div><div>The peptidoglycan associated lipoprotein (Pal) is crucial in Gram-negative bacteria, participating in outer-membrane integrity and septal wall constriction during cell division. It is also implicated in pathogenesis by mediating sepsis and immune responses. Pal has been one of the most intensively studied vaccine targets and herein we report a structural characterization and functional analysis of <em>Escherichia coli</em> Pal (Ec.Pal), as a member of the peptidoglycan-binding protein (PGBP) family. Multidimensional solution NMR spectroscopy was employed to obtain backbone assignments for truncated and full-length constructs of Ec.Pal, revealing that these proteins adopt the characteristic secondary structure of the OmpA_C-like domain and that the core residues fold similarly to the crystal structure reported for a truncated protein (PDB <span><span>1OAP</span><svg><path></path></svg></span>). However, full-length Ec.Pal possesses a previously unobserved N-terminal α1-helix, which in conjunction with a 30-residue flexible N-terminal linker, distinguishes Ec.Pal from other PGBP members. Biophysical studies further demonstrated the role of this terminal region in mediating the dimerization of Ec.Pal, contrasting its behavior with other PGBPs. Moreover, our findings for an acylated version of Ec.Pal which was purified as a SMALP-complex, suggest that Ec.Pal can interact with membrane mimetics through the flexible N-terminal region as well. Additionally, the C-terminal domain of Ec.Pal was shown to bind peptidoglycan (PG) components and co-purify with the PG-precursor (PGp), highlighting its role in cell wall dynamics. These results contribute to understanding the structural basis of Ec.Pal's function in bacterial membrane biology and its potential as a therapeutic target.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184501"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146028296","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}

引用次数: 0

Biophysical approaches to antimicrobial peptide–membrane characterization 抗菌肽膜表征的生物物理方法。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-13 DOI: 10.1016/j.bbamem.2026.184499

A. Roldán , P. Fernández-García , V. Lladó , M. Torres , P.V. Escribá , M. Salvador-Castell

{"title":"Biophysical approaches to antimicrobial peptide–membrane characterization","authors":"A. Roldán , P. Fernández-García , V. Lladó , M. Torres , P.V. Escribá , M. Salvador-Castell","doi":"10.1016/j.bbamem.2026.184499","DOIUrl":"10.1016/j.bbamem.2026.184499","url":null,"abstract":"<div><div>Antimicrobial peptides (AMPs) represent a current strategy to develop new antibiotics against multi-resistant pathogens. The potential antibiotic activity of AMPs is related to their amphipathic properties and the presence of positively charged residues, which may interact with the negatively charged bacterial membranes. In contrast, they exhibit lower interaction with the eukaryotic, neutrally charged membranes. This is the primary reason AMPs can distinguish between eukaryotic and prokaryotic membranes.</div><div>AMPs are usually modified or designed <em><strong>de novo</strong></em>, and their properties can be changed by inserting specific amino acid residues into their sequence. To assist in the rational design of AMPs, it is helpful to explore the biophysical changes they may induce in target cell membranes. Therefore, bacterial and eukaryotic model lipid membranes have been extensively used for this purpose. Parameters such as selective binding, lipid membrane interactions, membrane packing, permeability, hydration, and restructuring facilitate the exploration of peptide regions of interest. These parameters can be studied using various physicochemical techniques, including differential scanning calorimetry, X-ray diffraction, nuclear magnetic resonance, and fluorescence spectroscopy.</div><div>This review aims to provide a practical guide to the main biophysical techniques used to explore the potential antibiotic activity of AMPs using model membranes, and to examine lipid-peptide interactions in order to define the mechanisms of action of these antimicrobial peptides. These techniques determine whether the peptide interacts specifically with bacterial membranes, the preferred bacterial target of a given AMP, the binding affinities of AMPs, potential pore formation and its geometry, and the impact of these interactions on both bacterial and eukaryotic membranes.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184499"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145987895","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}

引用次数: 0

Investigating the electrostatics underlying activation of the β 2 adrenergic receptor 研究β 2肾上腺素能受体激活的静电

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2026-01-16 DOI: 10.1016/j.bbamem.2026.184503

Julia M. Montgomery , Justin A. Lemkul

{"title":"Investigating the electrostatics underlying activation of the β 2 adrenergic receptor","authors":"Julia M. Montgomery , Justin A. Lemkul","doi":"10.1016/j.bbamem.2026.184503","DOIUrl":"10.1016/j.bbamem.2026.184503","url":null,"abstract":"<div><div>G-protein coupled receptors (GPCRs) are the largest family of membrane proteins in humans and represent critical targets for drug discovery efforts. Among GPCRs, the <span><math><mi>β</mi></math></span>-2 adrenergic receptor (<span><math><mi>β</mi></math></span> <sub>2</sub>AR) has served as a prototypical example of the protein family as well as an important target for pulmonary diseases. As such, much work has been done to investigate this GPCR experimentally and computationally. Many of the interactions that drive activation of <span><math><mi>β</mi></math></span> <sub>2</sub>AR are defined by electrostatics, emphasizing the need for robust simulations with accurate force field models. Only with recent advancements in computing capabilities and refined force fields has it become feasible to simulate this membrane protein on relevant time scales and with sufficiently accurate physical models. Here, we report outcomes of simulations with the Drude polarizable force field to explore the electrostatics underlying <span><math><mi>β</mi></math></span> <sub>2</sub>AR dynamics, marking the first application of explicit electronic polarization in this protein. We found that perturbation of intrinsic dipole moments in key microswitch residues associated with ligand binding is important for subtle conformational changes, resulting in different in conformational sampling compared to a nonpolarizable force field. The results of this study provide a new view of this common drug target with an emphasis on the role of electrostatics.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184503"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145973004","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}

引用次数: 0

Structural and dynamics of apoA-1 mimetic peptide lipid nanodisc assemblies: A molecular dynamics study 模拟apoA-1肽脂质纳米盘组装的结构和动力学：分子动力学研究。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2025-11-29 DOI: 10.1016/j.bbamem.2025.184495

Rohith Ravi , Evgeniy S. Salnikov , Burkhard Bechinger , Mounir Tarek

{"title":"Structural and dynamics of apoA-1 mimetic peptide lipid nanodisc assemblies: A molecular dynamics study","authors":"Rohith Ravi , Evgeniy S. Salnikov , Burkhard Bechinger , Mounir Tarek","doi":"10.1016/j.bbamem.2025.184495","DOIUrl":"10.1016/j.bbamem.2025.184495","url":null,"abstract":"<div><div>Apolipoprotein A-I (apoA-I) mimetic peptides, inspired by the principal protein component of high-density lipoprotein, self-assemble with lipids to form discoidal nanodiscs widely used in biomedical research and as versatile scaffolds for characterization of membrane proteins in structural biology. Here, we investigate the 14A apoA-I mimetic, quantifying its orientation around the lipid bilayer and identifying the interactions that are crucial for nanodisc stability and dynamics using all-atom molecular dynamics simulations. To assess model fidelity, we back-calculated solid-state NMR observables, namely <sup>15</sup>N chemical shifts and <sup>2</sup>H quadrupolar splittings from the trajectories and compared them with previously reported solid-state NMR data. The simulations support a dimeric, antiparallel, belt-like arrangement of 14A peptides around the discoidal bilayer, stabilized by <span><math><mrow><mi>π</mi><mo>−</mo><mi>π</mi></mrow></math></span> stacking between aromatic residues and by electrostatic and hydrophobic peptide–lipid interactions. These interactions yield structurally stable nanodiscs with pronounced heterogeneity in lipid ordering and bilayer thickness between the nanodisc center and rim. Collectively, our MD results provide atomistic evidence for previously hypothesized peptide–peptide and peptide–lipid interactions and clarify how amphipathic helices organize to form the rim of discoidal nanodiscs. These insights inform the rational design of apoA-I mimetics for biomedical applications and the optimization of nanodiscs as platforms for studying membrane proteins.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184495"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145653414","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}

引用次数: 0

Nanoscopic remodeling of lipid bilayers by cell-penetrating peptide penetratin 细胞穿透肽穿透素对脂质双层的纳米重塑。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2025-12-29 DOI: 10.1016/j.bbamem.2025.184496

Yasith Indigahawela Gamage, Jianjun Pan

{"title":"Nanoscopic remodeling of lipid bilayers by cell-penetrating peptide penetratin","authors":"Yasith Indigahawela Gamage, Jianjun Pan","doi":"10.1016/j.bbamem.2025.184496","DOIUrl":"10.1016/j.bbamem.2025.184496","url":null,"abstract":"<div><div>Cell-penetrating peptides (CPPs) such as penetratin are known to traverse lipid membranes, yet the nanoscale structural consequences of their membrane interactions remain incompletely understood. Using atomic force microscopy (AFM), we visualized penetratin-induced remodeling in supported lipid bilayers (SLBs), focusing on discrete POPC bilayer patches whose exposed edges sensitively report early structural changes. In POPC patches, penetratin first accumulated at patch boundaries, forming elevated peripheral rings, and at higher concentrations generated shallow nanoscale pits across the patch interior. Continuous POPC bilayers exhibited a closely parallel pathway—elevated protrusions at 1 μM penetratin and widespread nanoscale pore-like depressions at 2–4 μM—indicating that similar peptide–lipid structures form even without membrane edges. Bilayers containing anionic POPS showed greatly enhanced susceptibility, progressing from peripheral depressions and aggregates to full fragmentation into nanoscale lipid–peptide particles, whereas cholesterol-containing bilayers remained largely resistant, developing only a few isolated deep defects. Our findings reveal an array of penetratin-induced remodeling events shaped by membrane composition and geometry, providing new mechanistic insight into how penetratin modulates membrane structure at the nanoscale.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184496"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877506","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}

引用次数: 0

Mechanistic insight into the role of lipoglycopeptide drugs in hepatotoxicity 脂糖肽类药物在肝毒性中的作用机制。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-04-01 Epub Date: 2025-12-29 DOI: 10.1016/j.bbamem.2025.184497

Akash Kumar Jha , Vetriselvan Subramaniyan , Raj Gupta , Arabinda Saha , Ashutosh Kumar

{"title":"Mechanistic insight into the role of lipoglycopeptide drugs in hepatotoxicity","authors":"Akash Kumar Jha , Vetriselvan Subramaniyan , Raj Gupta , Arabinda Saha , Ashutosh Kumar","doi":"10.1016/j.bbamem.2025.184497","DOIUrl":"10.1016/j.bbamem.2025.184497","url":null,"abstract":"<div><div>Understanding how antibiotics interact with membranes is crucial for predicting their off-target effects, particularly hepatotoxicity. This work compares two clinically important glycopeptide antibiotics, Teicoplanin and Oritavancin, using an integrative approach that combines in vivo pathology, lipid biophysics, drug-lipid interactions by NMR spectroscopy, and molecular dynamics simulations. Despite causing little direct disruption to lipid membranes, Teicoplanin produced significant hepatotoxicity, including increased liver enzymes and histopathological loss. Teicoplanin localises at the membrane–aqueous interface, where it forms stable surface-level interactions that have the potential to periodically disrupt membrane-associated processes. On the other hand, due to its deep insertion into the bilayer core, Oritavancin exhibited a more benign hepatic profile, despite causing stronger membrane perturbation. Long-term cellular stress is probably mitigated by this embedded configuration, which facilitates less interaction with membrane receptors. These findings demonstrate that glycopeptide-induced hepatotoxicity is governed by the topology and duration of membrane interactions rather than simply by their magnitude. The study promotes a lipid-centric framework for the logical development of safer, membrane-active treatments and emphasises the value of lipid membrane models and atomistic simulations as predictive tools in early-stage drug evaluation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 2","pages":"Article 184497"},"PeriodicalIF":2.5,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145877442","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}

引用次数: 0

Study of the effects of phenolic acids and their triphenylphosphonium derivatives on the permeability and state of liposomal membrane, the functional activity of isolated rat liver mitochondria, and the survival of MCF-7 cells 酚酸及其三苯磷衍生物对脂质体膜通透性、状态、离体大鼠肝线粒体功能活性及MCF-7细胞存活的影响

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-01-01 Epub Date: 2025-10-12 DOI: 10.1016/j.bbamem.2025.184473

Mikhail V. Dubinin , Anna I. Ilzorkina , Anastasia D. Igoshkina , Natalia V. Mikina , Rezeda R. Khalitova , Nikita V. Penkov , Natalia V. Belosludtseva , Anna Y. Spivak , Konstantin N. Belosludtsev

{"title":"Study of the effects of phenolic acids and their triphenylphosphonium derivatives on the permeability and state of liposomal membrane, the functional activity of isolated rat liver mitochondria, and the survival of MCF-7 cells","authors":"Mikhail V. Dubinin , Anna I. Ilzorkina , Anastasia D. Igoshkina , Natalia V. Mikina , Rezeda R. Khalitova , Nikita V. Penkov , Natalia V. Belosludtseva , Anna Y. Spivak , Konstantin N. Belosludtsev","doi":"10.1016/j.bbamem.2025.184473","DOIUrl":"10.1016/j.bbamem.2025.184473","url":null,"abstract":"<div><div>This study shows the effects of phenolic acids (gallic, coumaric, caffeic, and ferulic) and their triphenylphosphonium (TPP<sup>+</sup>) derivatives on the state of liposomal membrane, the functioning of isolated rat liver mitochondria, and the survival of MCF-7 breast adenocarcinoma cells. It was demonstrated that alkyltriphenylphosphonium esters of phenolic acids in contrast to their parental compounds, increase liposome membrane permeability to sulforhodamine B without altering their phase state. These derivatives also exhibit uncoupling effects on oxidative phosphorylation, reducing membrane potential and stimulating oxygen consumption in mitochondria fueled by glutamate/malate (substrate for complex I of the respiratory chain) or succinate (substrate for complex II). In addition, the compounds reduced the ability of mitochondria to uptake and retain Ca<sup>2+</sup>, suggesting their influence on calcium homeostasis. Conjugation of phenolic acids with the TPP<sup>+</sup> moiety significantly enhanced their cytotoxic effects on MCF-7 cells. This study establishes a clear structure-activity relationship, demonstrating that conjugation with TPP<sup>+</sup> via an ester linker is an advantageous strategy for enhancing the mitochondrial targeting and bioactivity of phenolic acids compared to amide linkage or the parental compounds.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184473"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290780","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}

引用次数: 0

Effect of amyloid-beta 1–40 and 1–42 peptides on the lateral diffusion and signaling of receptor for advanced glycation endproducts (RAGE) 淀粉样蛋白- β 1-40和1-42肽对晚期糖基化终末产物（RAGE）受体横向扩散和信号传导的影响。

IF 2.5 3区生物学

Biochimica et biophysica acta. Biomembranes Pub Date : 2026-01-01 Epub Date: 2025-11-19 DOI: 10.1016/j.bbamem.2025.184485

Chamari S. Wijesooriya , Sharifur Rahman , Emily A. Smith

{"title":"Effect of amyloid-beta 1–40 and 1–42 peptides on the lateral diffusion and signaling of receptor for advanced glycation endproducts (RAGE)","authors":"Chamari S. Wijesooriya , Sharifur Rahman , Emily A. Smith","doi":"10.1016/j.bbamem.2025.184485","DOIUrl":"10.1016/j.bbamem.2025.184485","url":null,"abstract":"<div><div>The receptor for advanced glycation endproducts (RAGE) is a pattern recognition receptor that interacts with different ligands, including the amyloid-beta (Aβ) peptides, to initiate signaling pathways and create pro-inflammatory mediators. Receptor diffusion plays an important role in its functionality; for example, lateral mobility is needed for the assembly of signaling complexes. However, the effect of Aβ ligand binding on the diffusion of RAGE and its correlation with RAGE-mediated signaling have not been studied. This study investigated the impact of Aβ 1–40 and Aβ 1–42 on RAGE's lateral diffusion and MAPK signaling. Differing in length by only two amino acids, these two most prominent Aβ isoforms have differing cellular toxicities: Aβ 1–42 is considered the more toxic form. Single-particle tracking measurements showed that both Aβ 1–40 and Aβ 1–42 altered RAGE diffusion in HEK293 cells compared to a ligand untreated control, although the effects were different for each peptide. Aβ 1–42 treatment enhanced the activation of both p38 and p44/42 MAPKs via RAGE, whereas Aβ 1–40 treatment did not significantly increase p38 activation. These results are consistent with the greater toxicity of Aβ 1–42: p38 MAPK is often associated with stress-stimuli and inflammation whereas p44/42 MAPK is more commonly associated with growth factors and cell proliferation. The results show that differing cellular toxicities of Aβ 1–40 and Aβ 1–42 are also associated with divergent effects on RAGE diffusion and MAPK signal pathway activation.</div></div>","PeriodicalId":8831,"journal":{"name":"Biochimica et biophysica acta. Biomembranes","volume":"1868 1","pages":"Article 184485"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572673","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}

引用次数: 0