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1.
J Phys Chem B ; 128(28): 6816-6829, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-38959082

RESUMO

The effects of two ionic liquids (ILs), 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and 1-butyl-1-methyl pyrrolidinium tetrafluoroborate ([bmp]BF4), on a mixture of phospholipids (PLs) 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) (6:3:1, M/M/M, 70% PL) in combination with 30 mol % cholesterol (CHOL) were investigated in the form of a solvent-spread monolayer and bilayer (vesicle). Surface pressure (π)-area (A) isotherm studies, using a Langmuir surface balance, revealed the formation of an expanded monolayer, while the cationic moiety of the IL molecules could electrostatically and hydrophobically bind to the PLs on the palisade layer. Turbidity, dynamic light scattering (size, ζ-potential, and polydispersity index), electron microscopy, small-angle X-ray/neutron scattering, fluorescence spectroscopy, and differential scanning calorimetric studies were carried out to evaluate the effects of IL on the structural organization of bilayer in the vesicles. The ILs could induce vesicle aggregation by acting as a "glue" at lower concentrations (<1.5 mM), while at higher concentrations, the ILs disrupt the bilayer structure. Besides, ILs could result in the thinning of the bilayer, evidenced from the scattering studies. Steady-state fluorescence anisotropy and lifetime studies suggest asymmetric insertion of ILs into the lipid bilayer. MTT assay using human blood lymphocytes indicates the safe application of vesicles in the presence of ILs, with a minimal toxicity of up to 2.5 mM IL in the dispersion. These results are proposed to have applications in the field of drug delivery systems with benign environmental impact.


Assuntos
Líquidos Iônicos , Líquidos Iônicos/química , Imidazóis/química , Fosfolipídeos/química , Colesterol/química , Bicamadas Lipídicas/química , Propriedades de Superfície , 1,2-Dipalmitoilfosfatidilcolina/química
2.
Methods Enzymol ; 701: 1-46, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39025569

RESUMO

A widely known property of lipid membranes is their tendency to undergo a separation into disordered (Ld) and ordered (Lo) domains. This impacts the local structure of the membrane relevant for the physical (e.g., enhanced electroporation) and biological (e.g., protein sorting) significance of these regions. The increase in computing power, advancements in simulation software, and more detailed information about the composition of biological membranes shifts the study of these domains into the focus of classical molecular dynamics simulations. In this chapter, we present a versatile yet robust analysis pipeline that can be easily implemented and adapted for a wide range of lipid compositions. It employs Gaussian-based Hidden Markov Models to predict the hidden order states of individual lipids by describing their structure through the area per lipid and the average SCC order parameters per acyl chain. Regions of the membrane with a high correlation between ordered lipids are identified by employing the Getis-Ord local spatial autocorrelation statistic on a Voronoi tessellation of the lipids. As an example, the approach is applied to two distinct systems at a coarse-grained resolution, demonstrating either a strong tendency towards phase separation (1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DIPC), cholesterol) or a weak tendency toward phase separation (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PUPC), cholesterol). Explanations of the steps are complemented by coding examples written in Python, providing both a comprehensive understanding and practical guidance for a seamless integration of the workflow into individual projects.


Assuntos
Bicamadas Lipídicas , Simulação de Dinâmica Molecular , Bicamadas Lipídicas/química , Fosfatidilcolinas/química , Cadeias de Markov , Software , Lipídeos de Membrana/química , Microdomínios da Membrana/química , 1,2-Dipalmitoilfosfatidilcolina/química
3.
Langmuir ; 40(26): 13583-13595, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38907731

RESUMO

The growing reliance on pesticides for pest management in agriculture highlights the need for new analytical methods to detect these substances in food and water. Our research introduces a SPRWG-(C18H37) lipopeptide (LP) as a functional analog of acetylcholinesterase (AChE) for glyphosate detection in environmental samples using phosphatidylcholine (PC) monolayers. This LP, containing hydrophilic amino acids linked to an 18-carbon aliphatic chain, alters lipid assembly properties, leading to a more flexible system. Changes included reduced molecular area and peak pressure in Langmuir adsorption isotherms. Small angle X-ray scattering (SAXS) and atomic force microscopy (AFM) analyses provided insights into the LP's structural organization within the membrane and its interaction with glyphosate (PNG). Structural and geometric parameters, as derived from in silico molecular dynamics simulations (MD), substantiated the impact of LP on the monolayer structure and the interaction with PNG. Notably, the presence of the LP and glyphosate increased charge transfer resistance, indicating strong adherence of the monolayer to the indium tin oxide (ITO) surface and effective pesticide interaction. A calibration curve for glyphosate concentration adjustment revealed a detection limit (LOD) of 24 nmol L-1, showcasing the high sensitivity of this electrochemical biosensor. This LOD is significantly lower than that of a similar colorimetric biosensor in aqueous media with a detection limit of approximately 0.3 µmol L-1. Such an improvement in sensitivity likely stems from adding a polar residue to the amino acid chain of the LP.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Glicina , Glifosato , Lipopeptídeos , Simulação de Dinâmica Molecular , Glicina/química , Glicina/análogos & derivados , Glicina/análise , 1,2-Dipalmitoilfosfatidilcolina/química , Lipopeptídeos/química , Lipopeptídeos/análise , Água/química , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/química , Propriedades de Superfície
4.
J Chem Inf Model ; 64(13): 5242-5252, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38912752

RESUMO

Biological membranes play key roles in cellular compartmentalization, structure, and its signaling pathways. At varying temperatures, individual membrane lipids sample from different configurations, a process that frequently leads to higher-order phase behavior and phenomena. Here, we present a persistent homology (PH)-based method for quantifying the structural features of individual and bulk lipids, providing local and contextual information on lipid tail organization. Our method leverages the mathematical machinery of algebraic topology and machine learning to infer temperature-dependent structural information on lipids from static coordinates. To train our model, we generated multiple molecular dynamics trajectories of dipalmitoyl-phosphatidylcholine membranes at varying temperatures. A fingerprint was then constructed for each set of lipid coordinates by PH filtration, in which interaction spheres were grown around the lipid atoms while tracking their intersections. The sphere filtration formed a simplicial complex that captures enduring key topological features of the configuration landscape using homology, yielding persistence data. Following fingerprint extraction for physiologically relevant temperatures, the persistence data were used to train an attention-based neural network for assignment of effective temperature values to selected membrane regions. Our persistence homology-based method captures the local structural effects, via effective temperature, of lipids adjacent to other membrane constituents, e.g., sterols and proteins. This topological learning approach can predict lipid effective temperatures from static coordinates across multiple spatial resolutions. The tool, called MembTDA, can be accessed at https://github.com/hyunp2/Memb-TDA.


Assuntos
Membrana Celular , Aprendizado de Máquina , Simulação de Dinâmica Molecular , Membrana Celular/metabolismo , Membrana Celular/química , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo , Temperatura , Redes Neurais de Computação , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química
5.
Soft Matter ; 20(25): 4935-4949, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38873752

RESUMO

Deformation of the cell membrane is well understood from the viewpoint of protein interactions and free energy balance. However, the various dynamic properties of the membrane, such as lipid packing and hydrophobicity, and their relationship with cell membrane deformation are unknown. Therefore, the deformation of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and oleic acid (OA) giant unilamellar vesicles (GUVs) was induced by heating and cooling cycles, and time-lapse analysis was conducted based on the membrane hydrophobicity and physical parameters of "single-parent" and "daughter" vesicles. Fluorescence ratiometric analysis by simultaneous dual-wavelength detection revealed the variation of different hydrophilic GUVs and enabled inferences of the "daughter" vesicle composition and the "parent" membrane's local composition during deformation; the "daughter" vesicle composition of OA was lower than that of the "parents", and lateral movement of OA was the primary contributor to the formation of the "daughter" vesicles. Thus, our findings and the newly developed methodology, named in situ quantitative membrane property-morphology relation (QmPMR) analysis, would provide new insights into cell deformation and accelerate research on both deformation and its related events, such as budding and birthing.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Membrana Celular , Interações Hidrofóbicas e Hidrofílicas , Ácido Oleico , Lipossomas Unilamelares , Lipossomas Unilamelares/química , Lipossomas Unilamelares/metabolismo , Ácido Oleico/química , 1,2-Dipalmitoilfosfatidilcolina/química , Membrana Celular/química
6.
Biochim Biophys Acta Biomembr ; 1866(5): 184332, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38740123

RESUMO

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-p-cymene ruthenium(II) complexes, [Ru(η6-p-cymene)P(3,5-C(CH3)3-C6H3)3Cl2] (1), [Ru(η6-p-cymene)P(3,5-CH3-C6H3)3Cl2] (2), [Ru(η6-p-cymene)P(4-CH3O-3,5-CH3-C6H2)3Cl2] (3), and [Ru(η6-p-cymene)P(4-CH3O-C6H4)3Cl2] (4), 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-sn-glycero-3-phosphocholine (DPPC) or 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 30 % cholesterol (Chol), 20 % 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and 10 % 1,2-dipalmitoyl-sn-glycero-3-phospho-l-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 (1) 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 (2) and (4) 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.


Assuntos
Membrana Celular , Cimenos , Rutênio , Cimenos/química , Cimenos/farmacologia , Membrana Celular/efeitos dos fármacos , Membrana Celular/química , Rutênio/química , Rutênio/farmacologia , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Monoterpenos/química , Monoterpenos/farmacologia , 1,2-Dipalmitoilfosfatidilcolina/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Fosfatidilcolinas/química
7.
Biochim Biophys Acta Biomembr ; 1866(5): 184334, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744417

RESUMO

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.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Colesterol , Ibuprofeno , Bicamadas Lipídicas , Ibuprofeno/química , Ibuprofeno/farmacologia , Colesterol/química , Colesterol/metabolismo , Estereoisomerismo , 1,2-Dipalmitoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Dicroísmo Circular , Microscopia de Força Atômica , Biomimética , Membranas Artificiais
8.
Int J Pharm ; 659: 124235, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38762165

RESUMO

Pulmonary delivery is an efficient route of administration to deliver cannabidiol (CBD) due to the high bioavailability and fast onset of action. The major formulation challenge is the poor aqueous solubility of CBD. This study aimed to produce inhalable CBD powders with enhanced solubility and characterise their solid-state properties. CBD was spray freeze dried with mannitol or trehalose dihydrate with and without dipalmitoylphosphatidylcholine (DPPC). All four powders had acceptable yields at > 70 % with porous and spherical particles. The two crystalline mannitol powders contained less residual solvent than both amorphous trehalose ones. The addition of DPPC did not affect the crystallinity and residual solvent level of the powders. Instead, DPPC made the particles more porous, decreased the particle size from 19-23 µm to 11-13 µm, and increased CBD solubility from 0.36 µg/mL to over 2 µg/mL. The two DPPC powders were dispersed from a low resistance RS01 inhaler, showing acceptable aerosol performance with emitted fractions at 91-93 % and fine particle fractions < 5 µm at 34-43 %. These formulations can be used as a platform to deliver CBD and other cannabinoids by inhalation.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Aerossóis , Canabidiol , Liofilização , Tamanho da Partícula , Pós , Solubilidade , 1,2-Dipalmitoilfosfatidilcolina/química , Canabidiol/química , Canabidiol/administração & dosagem , Administração por Inalação , Manitol/química , Trealose/química , Excipientes/química , Porosidade , Química Farmacêutica/métodos
9.
FEBS J ; 291(14): 3191-3210, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38602252

RESUMO

Adaptation to hypoxia has attracted much public interest because of its clinical significance. However, hypoxic adaptation in the body is complicated and difficult to fully explore. To explore previously unknown conserved mechanisms and key proteins involved in hypoxic adaptation in different species, we first used a yeast model for mechanistic screening. Further multi-omics analyses in multiple species including yeast, zebrafish and mice revealed that glycerophospholipid metabolism was significantly involved in hypoxic adaptation with up-regulation of lysophospholipid acyltransferase (ALE1) in yeast, a key protein for the formation of dipalmitoyl phosphatidylcholine [DPPC (16:0/16:0)], which is a saturated phosphatidylcholine. Importantly, a mammalian homolog of ALE1, lysophosphatidylcholine acyltransferase 1 (LPCAT1), enhanced DPPC levels at the cell membrane and exhibited the same protective effect in mammalian cells under hypoxic conditions. DPPC supplementation effectively attenuated growth restriction, maintained cell membrane integrity and increased the expression of epidermal growth factor receptor under hypoxic conditions, but unsaturated phosphatidylcholine did not. In agreement with these findings, DPPC treatment could also repair hypoxic injury of intestinal mucosa in mice. Taken together, ALE1/LPCAT1-mediated DPPC formation, a key pathway of glycerophospholipid metabolism, is crucial for cell viability under hypoxic conditions. Moreover, we found that ALE1 was also involved in glycolysis to maintain sufficient survival conditions for yeast. The present study offers a novel approach to understanding lipid metabolism under hypoxia and provides new insights into treating hypoxia-related diseases.


Assuntos
1-Acilglicerofosfocolina O-Aciltransferase , Membrana Celular , Glicerofosfolipídeos , Animais , 1-Acilglicerofosfocolina O-Aciltransferase/metabolismo , 1-Acilglicerofosfocolina O-Aciltransferase/genética , Camundongos , Membrana Celular/metabolismo , Glicerofosfolipídeos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Humanos , Adaptação Fisiológica/genética , Hipóxia/metabolismo , Hipóxia/genética , Peixe-Zebra/metabolismo , Peixe-Zebra/genética , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , Mucosa Intestinal/metabolismo
10.
Biochim Biophys Acta Biomembr ; 1866(5): 184328, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38688404

RESUMO

The interaction of L-Phe with the membrane components, i.e., lipids and proteins, has been discussed in the current literature due to the interest to understand the effect of single amino acids in relation to the formation of amyloid aggregates. In the present work, it is shown that L-Phe interacts with 9:1 DMPC (1,2-dimyristoyl-sn-glycero-3 phosphocholine)/DPPC (1,2-dipalmitoyl-sn-glycero-3 phosphocholine) mixtures but not in the 1:9 one. An important observation is that the interaction disappears when DPPC is replaced by diether PC (2-di-O-hexadecyl-sn-glycero-3-phosphocholine) a lipid lacking carbonyl groups (CO). This denotes that CO groups may interact specifically with L-Phe in accordance with the appearance of a new peak observed by Infrared spectroscopy (FTIR-ATR). The interaction of L-Phe affects the compressibility pattern of the 9:1 DMPC/DPPC mixture which is congruent with the changes observed by Raman spectra. The specific interaction of L-Phe with CO, propagates to phosphate and choline groups in this particular mixture as analyzed by FTIR-ATR spectroscopy and is absent when DMPC is dopped with diether PC.


Assuntos
Dimiristoilfosfatidilcolina , Fenilalanina , Fenilalanina/química , Fenilalanina/metabolismo , Dimiristoilfosfatidilcolina/química , Espectroscopia de Infravermelho com Transformada de Fourier , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Lipídeos de Membrana/química , Lipídeos de Membrana/metabolismo
11.
J Am Chem Soc ; 146(19): 13151-13162, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38687869

RESUMO

The nanoscopic layer of water that directly hydrates biological membranes plays a critical role in maintaining the cell structure, regulating biochemical processes, and managing intermolecular interactions at the membrane interface. Therefore, comprehending the membrane structure, including its hydration, is essential for understanding the chemistry of life. While cholesterol is a fundamental lipid molecule in mammalian cells, influencing both the structure and dynamics of cell membranes, its impact on the structure of interfacial water has remained unknown. We used surface-specific vibrational sum-frequency generation spectroscopy to study the effect of cholesterol on the structure and hydration of monolayers of the lipids 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and egg sphingomyelin (SM). We found that for the unsaturated lipid DOPC, cholesterol intercalates in the membrane without significantly changing the orientation of the lipid tails and the orientation of the water molecules hydrating the headgroups of DOPC. In contrast, for the saturated lipids DPPC and SM, the addition of cholesterol leads to clearly enhanced packing and ordering of the hydrophobic tails. It is also observed that the orientation of the water hydrating the lipid headgroups is enhanced upon the addition of cholesterol. These results are important because the orientation of interfacial water molecules influences the cell membranes' dipole potential and the strength and specificity of interactions between cell membranes and peripheral proteins and other biomolecules. The lipid nature-dependent role of cholesterol in altering the arrangement of interfacial water molecules offers a fresh perspective on domain-selective cellular processes, such as protein binding.


Assuntos
Membrana Celular , Colesterol , Água , Colesterol/química , Água/química , Membrana Celular/química , Membrana Celular/metabolismo , Fosfatidilcolinas/química , Esfingomielinas/química , 1,2-Dipalmitoilfosfatidilcolina/química
12.
Nanoscale ; 16(17): 8533-8545, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38595322

RESUMO

Lipid coating is considered a versatile strategy to equip nanoparticles (NPs) with a biomimetic surface coating, but the membrane properties of these nanoassemblies remain in many cases insufficiently understood. In this work, we apply C-Laurdan generalized polarization (GP) measurements to probe the temperature-dependent polarity of hybrid membranes consisting of a lipid monolayer adsorbed onto a polylactic acid (PLA) polymer core as function of lipid composition and compare the behavior of the lipid coated NPs (LNPs) with that of liposomes assembled from identical lipid mixtures. The LNPs were generated by nanoprecipitation of the polymer in aqueous solutions containing two types of lipid mixtures: (i) cholesterol, dipalmitoylphosphatidylcholine (DPPC), and the ganglioside GM3, as well as (ii) dioleoylphosphatidylcholine (DOPC), DPPC and GM3. LNPs were found to exhibit more distinct and narrower phase transitions than corresponding liposomes and to retain detectable phase transitions even for cholesterol or DOPC concentrations that yielded no detectable transitions in liposomes. These findings together with higher GP values in the case of the LNPs for temperatures above the phase transition temperature indicate a stabilization of the membrane through the polymer core. LNP binding studies to GM3-recognizing cells indicate that differences in the membrane fluidity affect binding avidity in the investigated model system.


Assuntos
Lipossomos , Fluidez de Membrana , Nanopartículas , Poliésteres , Poliésteres/química , Nanopartículas/química , Lipossomos/química , Colesterol/química , Polímeros/química , 1,2-Dipalmitoilfosfatidilcolina/química , Ácido Láctico/química , Lipídeos/química , Temperatura , Gangliosídeo G(M3)/química
13.
Langmuir ; 40(15): 7883-7895, 2024 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-38587263

RESUMO

N-Acylated amino acids and neurotransmitters in mammals exert significant biological effects on the nervous system, immune responses, and vasculature. N-Acyl derivatives of γ-aminobutyric acid (N-acyl GABA), which belong to both classes mentioned above, are prominent among them. In this work, a homologous series of N-acyl GABAs bearing saturated N-acyl chains (C8-C18) have been synthesized and characterized with respect to self-assembly, thermotropic phase behavior, and supramolecular organization. Differential scanning calorimetric studies revealed that the transition enthalpies and entropies of N-acyl GABAs are linearly dependent on the acyl chain length. The crystal structure of N-tridecanoyl GABA showed that the molecules are packed in bilayers with the acyl chains aligned parallel to the bilayer normal and that the carboxyl groups from opposite layers associate to form dimeric structures involving strong O-H···O hydrogen bonds. In addition, N-H···O and C-H···O hydrogen bonds between amide moieties of adjacent molecules within each layer stabilize the molecular packing. Powder X-ray diffraction studies showed odd-even alternation in the d spacings, suggesting that the odd chain and even chain compounds pack differently. Equimolar mixtures of N-palmitoyl GABA and dipalmitoylphosphatidylcholine (DPPC) were found to form stable unilamellar vesicles with diameters of ∼300-340 nm, which could encapsulate doxorubicin, an anticancer drug, with higher efficiency and better release characteristics than DPPC liposomes at physiologically relevant pH. These liposomes exhibit faster release of doxorubicin at acidic pH (<7.0), indicating their potential utility as drug carriers in cancer chemotherapy.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Lipossomos , Animais , 1,2-Dipalmitoilfosfatidilcolina/química , Termodinâmica , Doxorrubicina , Ácido gama-Aminobutírico , Varredura Diferencial de Calorimetria , Bicamadas Lipídicas/química , Mamíferos
14.
J Agric Food Chem ; 72(17): 9828-9841, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38639269

RESUMO

Understanding the transport mechanism of the peptide Asn-Cys-Trp (NCW) is crucial to improving its intestinal absorption and bioavailability. This study investigated the absorption of NCW through Caco-2 cell monolayers and its interaction with the DPPC bilayers. Results revealed that after a 3 h incubation, the Papp (AP-BL) and Papp (BL-AP) values of NCW at a concentration of 5 mmol/L were (22.24 ± 4.52) × 10-7 and (6.63 ± 2.31) × 10-7 cm/s, respectively, with the transport rates of 1.59 ± 0.32 and 0.62 ± 0.20%, indicating its moderate absorption. NCW was found to be transported via PepT1 and paracellular transport pathways, as evidenced by the significant impact of Gly-Pro and cytochalasin D on the Papp values. Moreover, NCW upregulated ZO-1 mRNA expression. Further investigation of the ZO-1-mediated interaction between NCW and tight junction proteins will contribute to a better understanding of the paracellular transport mechanism of NCW. The interaction between NCW and the DPPC bilayers was predominantly driven by entropy. NCW permeated the bilayers through electrostatic, hydrogen bonding, and hydrophobic interactions, resulting in increased fluidity, flexibility, and disorder as well as phase transition and phase separation of the bilayers.


Assuntos
Anti-Hipertensivos , Humanos , Células CACO-2 , Transporte Biológico , Anti-Hipertensivos/química , Anti-Hipertensivos/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , 1,2-Dipalmitoilfosfatidilcolina/metabolismo , Difusão , Proteína da Zônula de Oclusão-1/metabolismo , Proteína da Zônula de Oclusão-1/genética , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo
15.
J Phys Chem Lett ; 15(16): 4408-4415, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38625684

RESUMO

Probing protein-membrane interactions is vital for understanding biological functionality for various applications such as drug development, targeted drug delivery, and creation of functional biomaterials for medical and industrial purposes. In this study, we have investigated interaction of Human Serum Albumin (HSA) with two different lipids, dipalmitoylphosphatidylglycerol (dDPPG) and dipalmitoylphosphatidylcholine (dDPPC), using Vibrational Sum Frequency Generation spectroscopy at different membrane fluidity values. In the liquid-expanded (LE) state of the lipid, HSA (at pH 3.5) deeply intercalated lipid chains through a combination of electrostatic and hydrophobic interactions, which resulted in more ordering of the lipid chains. However, in the liquid-condensed (LC) state, protein intercalation is decreased due to tighter lipid packing. Moreover, our findings revealed distinct differences in HSA's interaction with dDPPG and dDPPC lipids. The interaction with dDPPC remained relatively weak compared to dDPPG. These results shed light on the significance of protein mediated changes in lipid characteristics, which hold considerable implications for understanding membrane protein behavior, lipid-mediated cellular processes, and lipid-based biomaterial design.


Assuntos
1,2-Dipalmitoilfosfatidilcolina , Fluidez de Membrana , Fosfatidilgliceróis , Humanos , Fosfatidilgliceróis/química , Fosfatidilgliceróis/metabolismo , 1,2-Dipalmitoilfosfatidilcolina/química , Interações Hidrofóbicas e Hidrofílicas , Albumina Sérica Humana/química , Albumina Sérica Humana/metabolismo , Eletricidade Estática
16.
Chem Biodivers ; 21(6): e202400348, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38616166

RESUMO

The immobilization of proteins on the surface of carriers is challenging due to the loss of protein structure and function in this process. Here, we report the development of the protein immobilization on the surface of the metallated-porphyrin complex in the porphysome nanocarrier. The conjugated Ni-porphyrin to fatty acid (as a tail) has been synthesized and independently placed at the depth of the bilayer center of Dipalmitoylphosphatidylcholine (DPPC) in which the Ni-porphyrin was at the polar region of the membrane and is thus superficial. This porphysome (DPPC: Ni-porphyrin, 4 : 1 mole ratio) was formed by supramolecular self-assembly with a diameter of 173±7 nm and zeta potential -8.5±3.4 mv, which exhibited no significant toxicity at the experimental concentrations and acceptable cellular uptake on MCF-7 cells. The physicochemical properties and specific protein binding sites of the firefly luciferase as a model protein into the porphysome (1 : 2 mole ratio) show the conjugation efficiency about 80 % and the conformation of protein was completely maintained. Furthermore, bioluminescence assay and SDS-PAGE confirmed the preservation of protein function. The stabilized platform of porphyrin-lipid structure can potentially improve the efficacy of protein functionality for a particular display, shifting porphysomes from a simple carrier to a therapeutic agent.


Assuntos
Porfirinas , Humanos , Sítios de Ligação/efeitos dos fármacos , Porfirinas/química , Porfirinas/farmacologia , Células MCF-7 , Portadores de Fármacos/química , Nanomedicina Teranóstica , Nanopartículas/química , Sobrevivência Celular/efeitos dos fármacos , 1,2-Dipalmitoilfosfatidilcolina/química , Sistemas de Liberação de Medicamentos , Tamanho da Partícula
17.
Mol Pharm ; 21(4): 1768-1776, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38381374

RESUMO

A better molecular understanding of the temperature-triggered drug release from lysolipid-based thermosensitive liposomes (LTSLs) is needed to overcome the recent setbacks in developing this important drug delivery system. Enhanced drug release was previously rationalized in terms of detergent-like effects of the lysolipid monostearyl lysophosphatidylcholine (MSPC), stabilizing local membrane defects upon LTSL lipid melting. This is highly surprising and here referred to as the 'lysolipid paradox,' because detergents usually induce the opposite effect─they cause leakage upon freezing, not melting. Here, we aim at better answers to (i) why lysolipid does not compromise drug retention upon storage of LTSLs in the gel phase, (ii) how lysolipids can enhance drug release from LTSLs upon lipid melting, and (iii) why LTSLs typically anneal after some time so that not all drug gets released. To this end, we studied the phase transitions of mixtures of dipalmitoylphosphatidylcholine (DPPC) and MSPC by a combination of differential scanning and pressure perturbation calorimetry and identified the phase structures with small- and wide-angle X-ray scattering (SAXS and WAXS). The key result is that LTSLs, which contain the standard amount of 10 mol % MSPC, are at a eutectic point when they release their cargo upon melting at about 41 °C. The eutectic present below 41 °C consists of a MSPC-depleted gel phase as well as small domains of a hydrocarbon chain interdigitated gel phase containing some 30 mol % MSPC. In these interdigitated domains, the lysolipid is stored safely without compromising membrane integrity. At the eutectic temperature, both the MSPC-depleted bilayer and interdigitated MSPC-rich domains melt at once to fluid bilayers, respectively. Intact, fluid membranes tolerate much less MSPC than interdigitated domains─where the latter have melted, the high local MSPC content causes transient pores. These pores allow for fast drug release. However, these pores disappear, and the membrane seals again as the MSPC distributes more evenly over the membrane so that its local concentration decreases below the pore-stabilizing threshold. We provide a pseudobinary phase diagram of the DPPC-MSPC system and structural and volumetric data for the interdigitated phase.


Assuntos
Bicamadas Lipídicas , Lipossomos , Lipossomos/química , Bicamadas Lipídicas/química , Espalhamento a Baixo Ângulo , Varredura Diferencial de Calorimetria , Difração de Raios X , 1,2-Dipalmitoilfosfatidilcolina/química
18.
Small ; 20(26): e2306707, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38247201

RESUMO

In living organisms, carotenoids are incorporated in biomembranes, remarkably modulating their mechanical characteristics, fluidity, and permeability. Significant resonance enhancement of Raman optical activity (ROA) signals of carotenoid chiral aggregates makes resonance ROA (RROA), a highly selective tool to study exclusively carotenoid assemblies in model membranes. Hence, RROA is combined with electronic circular dichroism (ECD), dynamic light scattering (DLS), molecular dynamics, and quantum-chemical calculations to shed new light on the carotenoid aggregation in dipalmitoylphosphatidylcholine (DPPC) liposomes. Using representative members of the carotenoid family: apolar α-carotene and more polar fucoxanthin and zeaxanthin, the authors demonstrate that the stability of carotenoid aggregates is directly linked with their orientation in membranes and the monomer structures inside the assemblies. In particular, polyene chain distortion of α-carotene molecules is an important feature of J-aggregates that show increased orientational freedom and stability inside liposomes compared to H-assemblies of more polar xanthophylls. In light of these results, RROA emerges as a new tool to study active compounds and drugs embedded in membranes.


Assuntos
Carotenoides , Lipossomos , Análise Espectral Raman , Análise Espectral Raman/métodos , Carotenoides/química , Lipossomos/química , Simulação de Dinâmica Molecular , Dicroísmo Circular , 1,2-Dipalmitoilfosfatidilcolina/química , Xantofilas/química
19.
Chem Phys Lipids ; 258: 105365, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38092233

RESUMO

Layers of pulmonary lipids on an aqueous substrate at non-equilibrium conditions can decrease the surface tension of water to quite low values. This is connected with different relaxation processes occurring at the interface and the associated changes in the surface layer structure. Results of measurements by the combination of methods like surface rheology, ellipsometry, Brewster angle microscopy, and IRRAS for spread layers of lipid mixtures open a possibility to specify the dynamics of structural changes at conditions close to the physiological state. At sufficiently low surface tension values (below 5 mN/m) significant changes in the ellipsometric signal were observed for pure DPPC layers, which can be related to a transition from 2D to 3D structures caused by the layer folding. The addition of other lipids can accelerate the relaxation processes connected with squeezing-out of molecules or multilayer stacks formation hampering thereby a decrease of surface tension down to low values corresponding to the folding of the monolayer.


Assuntos
Pulmão , Microscopia , Tensão Superficial , Pulmão/química , Lipídeos/química , Propriedades de Superfície , Água/química , 1,2-Dipalmitoilfosfatidilcolina/química
20.
Chem Phys Lipids ; 259: 105366, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38081501

RESUMO

The thermal behavior of unilamellar vesicles has been revisited with differential scanning calorimetry to address the issue of whether it is essential to include interactions between neighboring bilayers in theories and simulations of the ripple phase. The issue focuses on the lower, aka pretransition, and the ripple phase that clearly exists between the lower and main transitions in multilamellar vesicles (MLV). We find anomalous thermal behavior in unilamellar vesicles (ULV) beginning at the same temperature as the lower transition in MLVs, but this feature is considerably broadened and somewhat weaker compared to the lower transition in MLVs. We ascribe this to the difficulty of packing a regular ripple pattern on small spheres. In agreement with a few reports of a ripple phase in direct images of single bilayers, we conclude that interactions between neighboring bilayers are not essential for the ripple phase in lipid bilayers.


Assuntos
Bicamadas Lipídicas , Lipossomas Unilamelares , Bicamadas Lipídicas/química , Calorimetria , Temperatura , Varredura Diferencial de Calorimetria , 1,2-Dipalmitoilfosfatidilcolina/química
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