Lipid Phase Research Articles

Using kraft lignin nanoparticles for the stabilization of nano/micro wax carriers

Due to its amphiphilic structure, lignin has the potential to stabilize emulsions via adsorption at the oil/water interface. By converting lignin into nanoparticles, we can significantly enhance its emulsion-stabilizing capabilities through a Pickering-type stabilization mechanism. Two essential elements may be modified to fine-tune emulsion stability: the size of the lignin nanoparticles (LNPs) and the physicochemical nature of the lipid phase. In this context, we highlight the behavior and utility of unmodified LNPs in the preparation of Pickering emulsions made up of water and a complex bio-based pharmaceutical-grade wax that can be used for the formulation of lipid carriers. As a proof-of-concept, we employ the developed Pickering emulsions to encapsulate indocyanine green (ICG), an FDA-approved dye commonly used in medical imaging applications. We demonstrate that ultra-small LNPs are well-suited for the colloidal stabilization of pharmaceutical wax ester micro beads. This stabilization does not require any lignin modification. Additionally, we present evidence that our new lipid/lignin hybrid carrier has potential as a new drug delivery system.

Polar Glycerolipids and Membrane Lipid Rafts.

Current understanding of the structure and functioning of biomembranes is impossible without determining the mechanism of formation of membrane lipid rafts. The formation of liquid-ordered and disordered phases (Lo and Ld) and lipid rafts in membranes and their simplified models is discussed. A new consideration of the processes of formation of lipid phases Lo and Ld and lipid rafts is proposed, taking into account the division of each of the glycerophospholipids into several groups. Generally accepted three-component schemes for modeling the membrane structure are critically considered. A four-component scheme is proposed, which is designed to more accurately assume the composition of lipids in the resulting Lo and Ld phases. The role of the polar head groups of phospholipids and, in particular, phosphatidylethanolamine is considered. The structure of membrane rafts and the possible absence of a clear boundary between the Lo and Ld phases are discussed.

Effect of carnosine on nitrosamine formation in gastric-simulated aqueous and lipid environments.

Nitrite salts are frequently utilized as meat additives to improve the quality and safety of processed meat products. However, these salts are associated with the formation of carcinogenic nitrosamines. Given its potential regulating effect on the formation of intermediate molecules, such as nitric oxide, it is hypothesized that carnosine, a meat constituent possessing antioxidant activity and other multiple health benefits, could dampen the formation of nitrosamines. The current study therefore assessed the effect of carnosine on nitrosamine formation in both a monophasic aqueous system and a biphasic water-lipid system simulating a gastric environment. In the monophasic system, relatively high levels of carnosine were required to significantly reduce the formation of different species of nitrosamine compared with the control (no carnosine). While higher levels of some nitrosamines were generated in both phases of the biphasic system, low carnosine concentrations significantly suppressed nitrosamine formation in the aqueous phase, while in the lipid phase, intermediate levels of carnosine were required. At higher carnosine levels, further reduction in nitrosamines was observed in the lipid phase. This study demonstrates the capacity of carnosine to reduce nitrosamine formation in aqueous and lipid environments and suggests the potential of dietary carnosine to lower the risks associated with the consumption of processed meat products. © 2024 His Majesty the King in Right of Canada and The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry. Reproduced with the permission of the Minister of Agriculture and Agri-Food Canada.

Effects of Lipid Phase Content on the Technological and Sensory Properties of O/W Emulsions Containing Bemotrizinol-Loaded Nanostructured Lipid Carriers

Different lipid phase ratios (12, 14, and 16% w/w) were assessed for their ability to affect the technological and sensory properties of O/W emulsions in which bemotrizinol (BMTZ), a broad-spectrum sunscreen agent, was incorporated free or loaded into nanostructured lipid nanocarriers (NLC) to reduce its release from the vehicle and, hence, its skin permeation. The following technological properties were evaluated in vitro: spreadability, viscosity, pH, occlusion factor, BMTZ release, and sun protection factor (SPF). Sensory attributes were assessed by panelists in three different phases: before/during pick-up, rub-in, and after application. Raising the lipid phase ratio led to an increase in viscosity (from 8017 ± 143 cPs to 16,444 ± 770 cPs) and to a corresponding decrease in spreadability (from 9.35 ± 0.21 cm to 7.50 ± 0.10 cm), while the incorporation of BMTZ-loaded NLC determined a decrease in the occlusion factor (from 47.75 ± 1.16 to 25.91 ± 1.57) and an increase in SPF (from 6% for formulations containing 12% lipid phase to 15% for formulations containing 16% lipid phase). No BMTZ release was observed from all emulsions. Sensory attributes were mainly affected by the lipid phase ratio. These results suggest that the lipid phase ratio and BMTZ incorporation into NLC could contribute to determining the technological and sensory properties of O/W emulsions.

Outcomes of dietary alpha-lipoic acid on testicular vascularization, steroid hormones, and seminal quality in aged Baladi bucks

BackgroundSenescence is accompanied by a progressive decrease in male reproductive performance, mainly due to oxidative stress and endothelial dysfunction. Alpha lipoic acid (ALA) is a potent antioxidant, that diffuses freely in aqueous and lipid phases, possessing anti-inflammatory and anti-apoptotic properties. This study aimed to examine the effects of supplemental dietary ALA on testicular hemodynamics (TH), circulating hormones, and semen quality in aged goats. Twelve Baladi bucks were divided into two groups (n = 6 each); the first fed a basic ration and served as a control group (CON), while the second received the basic ration supplemented with 600 mg ALA/ kg daily for consecutive eight weeks (ALA).ResultsThere were improvements in testicular blood flow in the ALA group evidenced by a lower resistance index (RI) and pulsatility index (PI) concurrent with higher pampiniform-colored areas/pixel (W3-W6). There were increases in testicular volume and decreases in echogenicity (W3-W5; ALA vs. CON). Compared to the CON, ALA-bucks had higher serum concentrations of testosterone, estradiol, and nitric oxide (W3-W5). There were enhancements in semen traits (progressive motility, viability, morphology, and concentration, alanine aminotransferase enzyme) and oxidative biomarkers (catalase, total antioxidant capacity, and malondialdehyde).ConclusionsALA dietary supplementation (600 mg/kg diet) improved aged bucks’ reproductive performance by enhancing the testicular volume, testicular hemodynamics, sex steroids, and semen quality.

Residual Membrane Fluidity in Mycobacterial Cell Envelope Layers under Extreme Conditions Underlines Membrane-Centric Adaptation.

One of the routes for adaptation to extreme environments is via remodeling of cell membrane structure, composition, and biophysical properties rendering a functional membrane. Collective studies suggest some form of membrane feedback in mycobacterial species that harbor complex lipids within the outer and inner cell wall layers. Here, we study the homeostatic membrane landscape of mycobacteria in response to high hydrostatic pressure and temperature triggers using high pressure fluorescence, mass and infrared spectroscopies, NMR, SAXS, and molecular dynamics simulations. Our findings reveal that mycobacterial membrane possesses unique and lipid-specific pressure-induced signatures that attenuate progression to highly ordered phases. Both inner and outer membrane layers exhibit phase coexistence of nearly identical lipid phases keeping residual fluidity over a wide range of temperature and pressure, but with different sensitivities. Lipidomic analysis of bacteria grown under pressure revealed lipidome remodeling in terms of chain length, unsaturation, and specific long-chained characteristic mycobacterial lipids, rendering a fluid bacterial membrane. These findings could help understand how bacteria may adapt to a broad spectrum of harsh environments by modulating their lipidome to select lipids that enable the maintenance of a fluid functional cell envelope.

Enhancing the stability and bio-accessibility of carotenoids extracted from canistel (Lucuma nervosa) via liposomes encapsulation

Canistel (Lucuma nervosa) is a valuable natural source of carotenoids, but their use in the food industry is hampered by low extraction efficiency, poor stability, and limited bio-accessibility. HPLC results showed that a deep eutectic solvent (DES) composed of D-menthol and canoic acid (Men-CaA) has significantly higher extraction yields for lycopene (498.66 ± 3.20 μg/mL DW) and β-carotene (6.43 ± 0.23 μg/mL DW) than corn oil. UV-VIS spectrophotometry combined with response surface methodology results confirmed that the best encapsulation efficiency of liposome for lycopene and β-carotene was attained in the temperature range of 30–70 °C, with the ratio of carotenoid extract to liposome of 1:25 (w/w), the ratio of phospholipids to cholesterol, and the ratio of aqueous phase to lipid phase of 2:1 (v/v). SEM analysis revealed that liposome-encapsulated carotenoid extract formed spherical structures with a uniform texture and rough surface. The ζ-potential assay confirmed the highest stability of liposomes at pH 7. FTIR spectroscopy indicated effective encapsulation of canistel-derived carotenoids by liposomes. Furthermore, liposomes encapsulation improved the thermal and storage stability and bio-accessibility of lycopene and β-carotene. Encapsulating canistel carotenoids in liposomes significantly enhances their stability and bio-accessibility, presenting a viable strategy for preserving the efficacy of food-based active ingredients.

Utilization of Box Behnken Design for the Development and Evaluation of Luliconazole-loaded Nanoemulgel

Pharmaceutical research is always looking for novel ways to distribute drugs and developing these methods to increase the effectiveness of existing medications. The physicochemical characteristics of the drug determine the dose form. Lipophilic API development is a result of recent discoveries in high-throughput screening. A topical broad-spectrum antifungal agent is luliconazole. Due to its lower water solubility, topical administration is limited, and topical absorption is confined. The stratum corneum’s lipid phase’s solubility of the medication also serves as a rate-limiting step for penetration. Because fungal infections impact the skin’s epidermis, dermis, and deeper layers, medicine administration must be tailored to target high drug concentrations at the layers of the epidermis and dermis

Limonene-enriched ultra-structural cubosomes to augment ocular delivery of a poorly water soluble anti-fungal drug: Fabrication, characterization, statistical optimization, in vivo corneal uptake and histopathological evaluation in rabbits

The target of this investigation was to obtain the composition of the optimized Fenticonazole nitrate (FCN)-loaded cubosomal formula that can prolong precorneal retention, increase corneal absorption, enhance corneal permeation, and anti-fungal efficacy of FCN. Cubosomes are bi-continuous structural vesicles fabricated using the hot emulsification technique in accordance with a 23-full factorial design. The selected fabrication factors were the concentration of the Lipid phase (X1), glyceryl monooleate: lipid phase stabilizer ratio (X2), and aqueous phase stabilizer types (X3). Whereas, the encapsulation efficiency percent (EE%), Mean particle size (PS), Polydispersity index (PDI), and Zeta potential (ZP) were chosen as measured responses. The numerical optimization criterion of the design expert software was utilized to select the optimized formula (Op) for extra investigations. The Op formula had EE% of 87.94 ± 0.7 %, PS of 249.75 ± 1.48 nm, and ZP of −34.25 ± 0.64 mV. The in vitro release study of the Op formula in comparison with FCN suspension showed a zero-order and controlled kinetic release behavior. Moreover, the results of the pH, refractive index, surface tension, and mucoadhesion study confirmed the superiority and the safety of the Op formula. Further, the ex vivo permeation study demonstrated a significant enhancement in the transcorneal permeation of the Op formula than FCN suspension by 2.69-fold. Besides, the in vivo corneal uptake confirmed the higher permeation of the Op formula in comparison with FCN suspension. Draize test and histopathological examination ensured the in vivo safety and tolerability of the Op formula. Overall, the previous findings ensured the efficacy of cubosomes in enhancing ocular retention, absorption, permeation, and bioavailability of FCN.

Extensive targeting of chemical space at the prime side of ketoamide inhibitors of rhomboid proteases by branched substituents empowers their selectivity and potency

Rhomboid intramembrane serine proteases have been implicated in several pathologies, and emerge as attractive pharmacological target candidates. The most potent and selective rhomboid inhibitors available to date are peptidyl α-ketoamides, but their selectivity for diverse rhomboid proteases and strategies to modulate it in relevant contexts are poorly understood. This gap, together with the lack of suitable in vitro models, hinders ketoamide development for relevant eukaryotic rhomboid enzymes. Here we explore the structure-activity relationship principles of rhomboid inhibiting ketoamides by medicinal chemistry and enzymatic in vitro and in-cell assays with recombinant rhomboid proteases GlpG, human mitochondrial rhomboid PARL and human RHBDL2. We use X-ray crystallography in lipidic cubic phase to understand the binding mode of one of the best ketoamide inhibitors synthesized here containing a branched terminal substituent bound to GlpG. In addition, to extend the interpretation of the co-crystal structure, we use quantum mechanical calculations and quantify the relative importance of interactions along the inhibitor molecule. These combined experimental analyses implicates that more extensive exploration of chemical space at the prime side is unexpectedly powerful for the selectivity of rhomboid inhibiting ketoamides. Together with variations in the peptide sequence at the non-prime side, or its non-peptidic alternatives, this strategy enables targeted tailoring of potent and selective ketoamides towards diverse rhomboid proteases including disease-relevant ones such as PARL and RHBDL2.

W/O/W emulsion-filled sodium alginate hydrogel beads for co-encapsulation of vitamins C and E: Insights into the fabrication, lipolysis, and digestion behavior

In this study, vitamins C and E were simultaneously encapsulated in water-in-oil-in-water (W/O/W) emulsion-filled sodium alginate (SA) hydrogel beads, as well as the effects of SA concentrations (0.5%, 1.0%, 1.5%, and 2.0%) on the structures and lipolysis the of hydrogel beads were investigated. With increasing SA concentration, the beads showed larger sizes, denser structures and better textures. The droplets tightly penetrated the gel network at high SA concentrations. Digestion behavior revealed the disintegrated intramolecular structure at low SA concentrations. The beads with 0.5% SA were fragmented, losing the initial shape during digestion in the intestinal fluid. Additionally, lipid phases were released as W/O/W and O/W emulsion droplets after digestion. However, the high SA concentration-containing beads exhibited a well-preserved morphological structure after digestion, and the release profiles of lipid phase were mainly O/W emulsion droplets. Furthermore, vitamins C and E encapsulated in the beads exhibited high bioaccessibility (vitamin C: 90.20% and vitamin E: 95.19%).

Understanding Aβ Peptide Binding to Lipid Membranes: A Biophysical Perspective.

Aβ peptides are known to bind neural plasma membranes in a process leading to the deposit of Aβ-enriched plaques. These extracellular structures are characteristic of Alzheimer's disease, the major cause of late-age dementia. The mechanisms of Aβ plaque formation and deposition are far from being understood. A vast number of studies in the literature describe the efforts to analyze those mechanisms using a variety of tools. The present review focuses on biophysical studies mostly carried out with model membranes or with computational tools. This review starts by describing basic physical aspects of lipid phases and commonly used model membranes (monolayers and bilayers). This is followed by a discussion of the biophysical techniques applied to these systems, mainly but not exclusively Langmuir monolayers, isothermal calorimetry, density-gradient ultracentrifugation, and molecular dynamics. The Methodological Section is followed by the core of the review, which includes a summary of important results obtained with each technique. The last section is devoted to an overall reflection and an effort to understand Aβ-bilayer binding. Concepts such as Aβ peptide membrane binding, adsorption, and insertion are defined and differentiated. The roles of membrane lipid order, nanodomain formation, and electrostatic forces in Aβ-membrane interaction are separately identified and discussed.

Fabrication and efficacy assessment of combination of brimonidine and ivermectin for treatment of papulopustular rosacea.

Rosacea is a chronic inflammatory, multifactorial disease for which combination therapy could be an effective treatment. In this study, we evaluate the effect of the combination therapy of brimonidine 0.33% and ivermectin 1% as a single cream for the treatment of papulopustular rosacea. A stable and appropriate formulation was prepared by adding the aqueous phase to the lipid phase while being stirred. The stability and physicochemical properties of the formulation were evaluated under accelerated conditions. Twelve patients (36-60 years) with mild to moderate papulopustular rosacea and a Demodex count of five or more were treated with the combination of brimonidine 0.33% and ivermectin 1% cream. Clinician's Erythema Assessment (CEA), Patients Self-Assessment (PSA), skin erythema (ΔE) and lightness (ΔL), and skin biophysical parameters including transepidermal water loss (TEWL), skin hydration, pH, and sebum content, as well as erythema and melanin index and ultrasound parameters, were measured before treatment and 4 and 8 weeks after. Adverse drug reactions were also recorded. CEA and PSA decreased significantly from 3 to 2 after 8 weeks, respectively (p-value = 0.014 for CEA and 0.010 for PSA). ΔE and ΔL, as well as skin erythema index and TEWL improved after 8 weeks of treatment (p < 0.05). Two patients withdrew from the study in the first week because of local adverse effects; one developed flushing following treatment and left the investigation after 4 weeks and another patient withdrew from the study after 4 weeks due to deciding to become pregnant. Eight-week treatment with the combination of brimonidine 0.33% and ivermectin 1% was shown to be effective for improvement of erythema and inflammatory lesions in mild to moderate papulopustular rosacea.

UV-B Radiation Disrupts Membrane Lipid Organization and Suppresses Protein Mobility of GmNARK in Arabidopsis.

While it is well known that plants interpret UV-B as an environmental cue and a potential stressor influencing their growth and development, the specific effects of UV-B-induced oxidative stress on the dynamics of membrane lipids and proteins remain underexplored. Here, we demonstrate that UV-B exposure notably increases the formation of ordered lipid domains on the plasma membrane (PM) and significantly alters the behavior of the Glycine max nodule autoregulation receptor kinase (GmNARK) protein in Arabidopsis leaves. The GmNARK protein was located on the PM and accumulated as small particles in the cytoplasm. We found that UV-B irradiation interrupted the lateral diffusion of GmNARK proteins on the PM. Furthermore, UV-B light decreases the efficiency of surface molecule internalization by clathrin-mediated endocytosis (CME). In brief, UV-B irradiation increased the proportion of the ordered lipid phase and disrupted clathrin-dependent endocytosis; thus, the endocytic trafficking and lateral mobility of GmNARK protein on the plasma membrane are crucial for nodule formation tuning. Our results revealed a novel role of low-intensity UV-B stress in altering the organization of the plasma membrane and the dynamics of membrane-associated proteins.

The influence of the chlorine atom on the biological activity of 2′-hydroxychalcone in relation to the lipid phase of biological membranes - Anticancer and antimicrobial activity

The study investigates the effect of the presence of a chlorine atom in the 2′-hydroxychalcone molecule on its interaction with model lipid membranes, in order to discern its potential pharmacological activity. Five chlorine derivatives of 2′-hydroxychalcone were synthesized and evaluated against liposomes composed of POPC and enriched with cationic (DOTAP) or anionic (POPG) lipids. The physicochemical properties of the compounds were initially simulated using SwissAdame software, revealing high lipophilicity (ilogP values: 2.79–2.90). The dynamic light scattering analysis of liposomes showed that chloro chalcones induce minor changes in the diameter of liposomes of different surface charges. Fluorescence quenching assays with a TMA-DPH probe demonstrated the strong ability of the compounds to interact with the lipid bilayer, with varying quenching capacities based on chlorine atom position. FTIR studies indicated alterations in carbonyl, phosphate, and choline groups, suggesting a transition area localization rather than deep penetration into the hydrocarbon chains. Additionally, dipole potential reduction was observed in POPC and POPC-POPG membranes, particularly pronounced by derivatives with a chlorine atom in the B ring. Antibacterial and antibiofilm assays revealed enhanced activity of derivatives with a chlorine atom compared to 2′-hydroxychalcone, especially against Gram-positive bacteria. The MIC and MBIC50 values showed increased efficacy in the presence of chlorine with 3′-5′-dichloro-2′-hydroxychalcone demonstrating optimal antimicrobial and antibiofilm activity. Furthermore, antiproliferative assays against breast cancer cell lines indicated higher activity of B-ring chlorine derivatives, particularly against MDA-MB-231 cells. In general, the presence of a chlorine atom in 2′-hydroxychalcone improves its pharmacological potential, with derivatives showing improved antimicrobial, antibiofilm, and antiproliferative activities, especially against aggressive breast cancer cell lines. These findings underscore the importance of molecular structure in modulating biological activity and highlight chalcones with a chlorine as promising candidates for further drug development studies.

Low drug load, high retention mometasone furoate cream with polyglyceryl − 3 oleate as a chemical enhancer: Formulation development, in vivo and in vitro evaluation and molecular mechanisms

The study aimed to create a low loading, high retention, easier to apply O/W mometasone furoate (MF) cream using a chemical enhancer (CE) approach to provide more options for patients with atopic dermatitis (AD) and to investigate molecular mechanisms of its increased release and retention. A Box-Behnken design determined the optimal formulation based on stability and in vitro skin retention. Evaluations included appearance, rheological properties, irritation, in vivo tissue distribution and pharmacodynamics. Molecular mechanisms of enhanced release were studied using high-speed centrifugation, molecular dynamics and rheology. The interaction between the CE, MF and skin was studied by tape stripping, CLSM, ATR-FTIR and SAXS. The formulation was optimized to contain 0.05% MF and used 10% polyglyceryl-3 oleate (POCC) as the CE. There was no significant difference from Elocon® cream in in vivo retention and pharmacodynamics but increased in vivo retention by 3.14-fold and in vitro release by 1.77-fold compared to the basic formulation. POCC reduced oil phase cohesive energy density, enhancing drug mobility and release. It disrupted skin lipid phases, aiding drug entry and formed hydrogen bonds, prolonging retention. This study highlights POCC as a CE in the cream, offering insights for semi-solid formulation development.

Cannabidiol and Aza-BODIPY Coencapsulation for Photodynamic Therapy Enhancement in Liver Cancer Cells.

Photodynamic therapy (PDT) and cannabidiol (CBD) have been explored for their potential in synergistic cancer treatment. In this study, we employed CBD oil as a lipid phase, encapsulated within AZB-I@Lec-T to create lipid-based nanoparticles. Here, CBD oil does two tasks: it acts as a pyroptosis agent to destroy liver cancer cells and as a lipid phase to dissolve the photosensitizer. It was expected that this system would offer synergistic therapy between CBD and PDT better than a single use of each treatment. With a series of in vitro experiments, the nanoparticles exhibited induced apoptosis in 68% of HepG2 cells treated with AZB-I@Lec-T@CBD and near-infrared (NIR)-light irradiation, reducing expression levels of antioxidant defense system genes. Furthermore, both components worked well in a submicromolar range when combined in our formulation. These results highlight the potential for amplifying primary cellular damage with the combination of PDT and CBD encapsulation, providing a promising therapeutic approach for liver cancer treatment guidelines.

Ultrasound treatment of crystalline oil-in-water emulsions stabilized by sodium caseinate: Impact on emulsion stability through altered crystallization behavior in the oil globules

Partial coalescence is a key factor contributing to the instability of crystalline oil-in-water emulsions in products like dressings and sauces, reducing shelf life. The intrinsic characteristics of semi-crystalline droplets, including solid fat content, fat crystal arrangement, and polymorphism, play a pivotal role in influencing partial coalescence, challenging prevention efforts even with emulsifiers like amphiphilic proteins. High-intensity ultrasound (HIU) has emerged as an efficient and cost-effective technology for manipulating bulk fat crystallization, thereby enhancing physical properties. This study specifically investigates the impact of HIU treatment on fat crystallization on protein-stabilized crystalline emulsions, utilizing palm olein stearin (POSt) as the lipid phase and sodium caseinate (NaCas) as the surfactant under various HIU powers (100, 150, 200, 300, and 400 W). Results show that increasing HIU power maintained the interfacial potential (−20 mV) provided by NaCas in the emulsions without significant differences. Higher HIU power induced the most stable polymorphic form (β) in the emulsions. Engagingly, the emulsions at 200 W exhibited better storage stability and slower partial coalescence kinetics. Semi-crystalline globules had more uniform and integral crystal clusters that were distributed tangentially near the droplet boundary, perhaps attributed to intermediate subcooling (40.4 °C) at 200 W. The acoustic energy of HIU significantly translates into thermal effects, influencing subcooling degrees as a dominant factor affecting crystallisation in the emulsions. This study establishes ultrasonic crystallization as a novel strategy for modifying the stability of emulsions containing fat crystals.

How Does the Antibiotic Amphotericin B Enter Membranes and What Does It Do There?

Amphotericin B is a popular antifungal antibiotic, but the exact way it works is still a matter of debate. Here, we used monolayers composed of phosphatidylcholine with ergosterol as a model of fungal lipid membranes to study drug incorporation from the aqueous phase and analyze the molecular reorganization of membranes underlying the biological activity of the antibiotic. The results show that the internalization of antibiotic molecules into membranes occurs only in the presence of ergosterol in the lipid phase. Comparison of images of solid-supported monolayers obtained by atomic force microscopy and lifetime imaging fluorescence microscopy shows the formation of intramembrane clusters of various sizes in the lipid phase, consisting mainly of antibiotic dimers and relatively large membrane pores (∼15 nm in diameter). The results reveal multiple modes of action of amphotericin B, acting simultaneously, each of which adversely affects the structural properties of the lipid membranes and their physiological functionality.

An analysis of the dipalmitoylphosphatidylcholine bilayer gel phases predicted with molecular dynamics simulations using force fields from the GROMOS family

Dipalmitoylphosphatidylcholine is a phospholipid of major importance for biological systems. Molecular dynamics simulation investigations of this lipid focused on their behavior at human body temperature (≈ 37 °C or 310 K). For some applications, however, it is necessary to study its properties at room temperature (≈ 25 °C or 298 K). A small difference in temperature at this range is responsible for a phase transition in the lipid bilayer. Therefore, molecular dynamics simulations are carried out applying six different force fields from the GROMOS family to compare the less ordered phase (liquid-crystalline phase) with a more ordered phase (gel phase) of the hydrated bilayer of dipalmitoylphosphatidylcholine formed at 323 K and 298 K, respectively. The analysis of the bilayer structural quantities is used to evaluate order and packing at the two temperatures. The area per lipid and deuterium order parameter results are in agreement with simulation results from the literature and are also compared with experimental data. These parameters, however, do not provide a clear picture of the low-temperature gel phase present in the simulations using the force fields from the GROMOS family. To address this, a strategy for computing the lipid phase nematic order parameter is proposed, and a reference gel phase is simulated using the CHARMM36 force field for comparison. The results are consistent with other structural quantities but reveal a level of order that is below the expected for an ordered gel phase for the GROMOS force fields. Visual inspection of the simulation trajectories suggests the presence of a ripple phase. Overall, the GROMOS 54A8 provides the best performance among the tested GROMOS force fields for both investigated temperatures, even lacking a proper representation of the ordered gel phase.