Membrane Fluidity Of Liposomes Research Articles

Triplet-Triplet Annihilation Upconverting Liposomes: Mechanistic Insights into the Role of Membranes in Two-Dimensional TTA-UC.

Triplet-triplet annihilation upconversion (TTA-UC) implemented in nanoparticle assemblies is of emerging interest in biomedical applications, including in drug delivery and imaging. As it is a bimolecular process, ensuring sufficient mobility of the sensitizer and annihilator to facilitate effective collision in the nanoparticle is key. Liposomes can provide the benefits of two-dimensional confinement and condensed concentration of the sensitizer and annihilator along with superior fluidity compared to other nanoparticle assemblies. They are also biocompatible and widely applied across drug delivery modalities. However, there are relatively few liposomal TTA-UC systems reported to date, so systematic studies of the influence of the liposomal environment on TTA-UC are currently lacking. Here, we report the first example of a BODIPY-based sensitizer TTA-UC system within liposomes and use this system to study TTA-UC generation and compare the relative intensity of the anti-Stokes signal for this system as a function of liposome composition and membrane fluidity. We report for the first time on time-resolved spectroscopic studies of TTA-UC in membranes. Nanosecond transient absorption data reveal the BODIPY-perylene dyad sensitizer has a long triplet lifetime in liposome with contributions from three triplet excited states, whose lifetimes are reduced upon coinclusion of the annihilator due to triplet-triplet energy transfer, to a greater extent than in solution. This indicates triplet energy transfer between the sensitizer and the annihilator is enhanced in the membrane system. Molecular dynamics simulations of the sensitizer and annihilator TTA collision complex are modeled in the membrane and confirm the co-orientation of the pair within the membrane structure and that the persistence time of the bound complex exceeds the TTA kinetics. Modeling also reliably predicted the diffusion coefficient for the sensitizer which matches closely with the experimental values from fluorescence correlation spectroscopy. The relative intensity of the TTA-UC output across nine liposomal systems of different lipid compositions was explored to examine the influence of membrane viscosity on upconversion (UC). UC showed the highest relative intensity for the most fluidic membranes and the weakest intensity for highly viscous membrane compositions, including a phase separation membrane. Overall, our study reveals that the co-orientation of the UC pair within the membrane is crucial for effective TTA-UC within a biomembrane and that the intensity of the TTA-UC output can be tuned in liposomal nanoparticles by modifying the phase and fluidity of the liposome. These new insights will aid in the design of liposomal TTA-UC systems for biomedical applications.

Carrier-Tumor Cell Membrane Interactions for Optimized Delivery of a Promising Drug, 4(RS)-4-F4t-Neuroprostane.

Nanomedicines engineered to deliver molecules with therapeutic potentials, overcoming drawbacks such as poor solubility, toxicity or a short half-life, are targeted towards their cellular destination either passively or through various elements of cell membranes. The differences in the physicochemical properties of the cell membrane between tumor and nontumor cells have been reported, but they are not systematically used for drug delivery purposes. Thus, in this study, a new approach based on a match between the liposome compositions, i.e., membrane fluidity, to selectively interact with the targeted cell membrane was used. Lipid-based carriers of two different fluidities were designed and used to deliver 4(RS)-4-F4t-Neuroprostane (F4t-NeuroP), a potential antitumor molecule derived from docosahexaenoic acid (DHA). Based on its hydrophobic character, F4t-NeuroP was added to the lipid mixture prior to liposome formation, a protocol that yielded over 80% encapsulation efficiency in both rigid and fluid liposomes. The presence of the active molecule did not modify the liposome size but increased the liposome negative charge and the liposome membrane fluidity, which suggested that the active molecule was accommodated in the lipid membrane. F4t-NeuroP integration in liposomes with a fluid character allowed for the selective targeting of the metastatic prostate cell line PC-3 vs. fibroblast controls. A significant decrease in viability (40%) was observed for the PC-3 cancer line in the presence of F4t-NeuroP fluid liposomes, whereas rigid F4t-NeuroP liposomes did not alter the PC-3 cell viability. These findings demonstrate that liposomes encapsulating F4t-NeuroP or other related molecules may be an interesting model of drug carriers based on membrane fluidity.

Comprehensive analysis of the influence of physicochemical properties and tumor-associated environments on liposome intratumoral penetration

Poor tumor penetration is the most significant barrier to the clinical translation of nanomedicines. Despite numerous studies, little is known about how the physicochemical properties and tumor-associated environments impact liposome intratumoral penetration from a multi-factorial perspective. Thus, we developed a set of model liposomes to explore the laws of their intratumoral penetration. Our comprehensive analysis revealed that zeta potential, membrane fluidity, and size of liposomes could influence their penetration in the peripheral, intermediate, or central areas of the tumor, respectively. Moreover, protein corona and stromal cells primarily impeded liposome penetration in the tumor periphery, while the vascular vessels had a similar effect in the tumor center. Our results also revealed a non-monotonic relationship, indicating that the best condition for a single factor may not necessarily be the optimal choice when considering all the factors. The preferred size, zeta potential, and membrane fluidity for excellent tumor penetration are within the ranges of 52-72nm, 16-24mV, and 230-320 mp, respectively. Our study provides a comprehensive understanding of the influence of physicochemical properties and tumor-associated environments on liposome intratumoral penetration, offering explicit guidance for the precise design and rational optimization of anti-tumor liposomes.

Impact of Vanadium Complexes with Tetradentate Schiff Base Ligands on the DPPC and EYL Liposome Membranes: EPR Studies

This paper investigates the effect of three vanadium complexes with Schiff base-type tetradentate ligands of general formula N,N′-1,2-cyclohexylenebis(3,5-dichlorosalicylideneiminate) (V1); LVCl2 (L = N,N′-1,2-cyclohexylenebis(5-chlorosalicylideneiminate) (V2); and N,N′-1,3propylenebis (salicylideneiminate) (V3) on the fluidity of liposome membranes obtained by the sonication of natural lecithin (EYL) and synthetic lecithin (DPPC). The study was carried out with TEMPO and 16DOXYL spin probes using the EPR technique. The results show that the effect of the complexes on the fluidity of liposomes whose membranes are in the liquid crystalline phase is much stronger as compared to the liposome membranes in the gel phase.

The Impact of Propanol, N-Butanol and Pentanol on Aqueous Dispersions of Sonicated Liposomes. EPR Study

Abstract This paper presents the effect of selected alcohols on the fluidity of liposome membranes obtained in sonication of DPPC lecithin. Using the EPR technique, the duality of propanol, n-butanol and pentanol on the behaviour of the aqueous dispersion of liposomes was demonstrated. It was shown that after exceeding a certain concentration, these alcohols initiate dispersion foaming, leading to phase separation: liposome dispersion - lipid foam. The influence of the shape of the molecule and the length of hydrocarbon chains on the effectiveness of destabilisation of the structure of lipid membranes was indicated.

Molecular chaperone function of three small heat-shock proteins from a model probiotic species

Small heat-shock proteins (sHSP) are ubiquitous ATP-independent chaperones that prevent irreversible aggregation of heat-damaged denaturing proteins. Lactiplantibacillus plantarum is a widespread Gram-positive bacterium with probiotic claims and vast potential for agro-food, biotechnological and biomedical applications. L. plantarum possesses a family of three sHSP, which were previously demonstrated to be involved in its stress tolerance mechanisms. Here, the three L. plantarum sHSP were heterologously expressed, purified and shown to have a chaperone activity in vitro, measuring their capacity to suppress protein aggregation, as assayed spectrophotometrically by light scattering. Their anti-aggregative capacity was found to be differently influenced by pH. Differences were also found relative to their holdase function and their capacity to modulate liposome membrane fluidity, suggesting interplays between them and indicating diversified activities. This is the first study assessing the chaperone action of sHSP from a probiotic model. The different roles of the three sHSP can increase L. plantarum’s capabilities to survive the various types of stress characterising the diverse habitats of this highly adaptable species. Reported evidence supports the interest in L. plantarum as one of the model species for bacteria that have three different sHSP-encoding genes in their genomes.

Possible Role of Bent Structure of Methylated Lithocholic Acid on Artificial and Plasma Membranes.

Bile acids form micelles that are essential for the absorption of dietary lipids. However, excessive bile acid micelles can disrupt the plasma membrane by removing phospholipids, resulting in cell death. We hypothesized that the bent geometrical structure of the steroid scaffold of bile acids decreases the lipid order (similar to unsaturated phospholipids with cis double bonds), disrupting the plasma membrane. Here, lithocholic acid (LCA), a bile acid, was methylated to prevent micellization. Methylated lithocholic acid (Me-LCA) was mixed with a thin phase-separated lipid bilayer comprising 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), and cholesterol (Chol). Me-LCA was not localized in the DPPC-rich rigid phase but localized in the DOPC-rich fluid phase, and excess Me-LCA did not affect the phase separation. Me-LCA is distributed in the plasma and organelle membranes. However, Me-LCA with bent structure did not affect the membrane properties, membrane fluidity, and hydrophobicity of liposomes composed of DOPC, DPPC, and Chol and also did not affect the proliferation of cells.

The Flavonoid Molecule Procyanidin Reduces Phase Separation in Model Membranes.

Procyanidin extracted from fruits, such as apples, has been shown to improve lipid metabolization. Recently, studies have revealed that procyanidin interacts with lipid molecules in membranes to enhance lipid metabolism; however, direct evidence of the interaction between procyanidin and lipid membranes has not been demonstrated. In this study, the phase behaviors and changes in the membrane fluidity of cell-sized liposomes containing apple procyanidin, procyanidin B2 (PB2), were demonstrated for the first time. Phase separation in 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC)/1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC)/cholesterol ternary membranes significantly decreased after the addition of PB2. The prospect of applying procyanidin content measurements, using the results of this study, to commercial apple juice was also assessed. Specifically, the PB2 concentrations were 50%, 33%, and 0% for pure apple juice, 2-fold diluted apple juice, and pure water, respectively. The results of the actual juice were correlated with PB2 concentrations and phase-separated liposomes ratios, as well as with the results of experiments involving pure chemicals. In conclusion, the mechanism through which procyanidin improves lipid metabolism through the regulation of membrane fluidity was established.

Divergent effects of cholesterol on the structure and fluidity of liposome and catanionic vesicle membranes.

Lipid-like ion-pair amphiphile vesicles, or catanionic vesicles, have emerged as potential drug carriers. The effects of cholesterol on the properties of catanionic vesicles have yet been systematically studied. Here, we compared the effects of cholesterol on the structures and fluidities of dipalmitoylphosphatidylcholine liposomes and catanionic vesicles with similar main transition temperatures (Tm ). For liposomes, fluorescence anisotropy (FA) thermograms reveal typical condensing and disordering effects of cholesterol above and below Tm respectively. In contrast, FA and molecular simulation data reveal that catanionic bilayers below Tm are more fluidic due to shorter alkyl chains. This leads to only condensing effects of cholesterol for catanionic vesicles at all temperatures. Our results provide important insights into the fabrication of catanionic vesicles as novel drug carriers.

The spatial arrangement of astaxanthin in bilayers greatly influenced the structural stability of DPPC liposomes

Liposomes are regarded as the ideal nanocarrier for concurrent or separate delivery of nutraceuticals in the food industries. Precise control of the structural stability is essential for the processing, storage, and nutrition delivery of liposomes. Astaxanthin was found to significantly affect the membrane stability of liposomes by inserting into the phospholipid bilayers in a similar way to cholesterol. Compared with cholesterol, astaxanthin could significantly improve the phase transition temperature, membrane fluidity, and membrane compactness of liposomes. Additionally, the membrane stability was well modulated by controlling the distribution patterns of astaxanthin (monomers, H- and J-aggregates) in bilayers. For instance, astaxanthin H-aggregates could endow the liposomal membrane with highest rigidity and compactness. Additionally, astaxanthin aggregates, especially J-aggregates could greatly improve storage stability of liposomes, thus providing a novel strategy to regulate and optimize the stability of liposomes for their diversified applications.

Enhancing the Endocytosis of Phosphatidylserine-Containing Liposomes through Tim4 by Modulation of Membrane Fluidity.

Phosphatidylserine (PS) is a unique lipid that is recognized by the endogenetic receptor, T-cell immunoglobulin mucin protein 4 (Tim4), and PS-containing liposomes have potential use in therapeutic applications. We prepared PS-containing liposomes of various lipid compositions and examined how lipid membrane fluidity affects PS recognition by Tim4 and the resulting endocytosis efficiency into Hela cells. Surface plasmon resonance and laurdan studies showed that increasing lipid membrane fluidity increased the stability of the PS-Tim4 interaction but hampered the entry of liposomes into cells. These results show that endocytosis efficiency is determined by balancing opposing forces induced by membrane fluidity. We found that inclusion of the zwitterionic helper lipid, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, into liposomes ensured efficient cellular internalization because the presence of this lipid provides an ideal balance of lipid fluidity and Tim4 affinity. The results showed that PS recognition by Tim4 and the resulting endocytosis efficiency can be maximized by modulating the membrane fluidity of liposomes by selecting a zwitterionic helper lipid. This study improves our understanding of how to rationally optimize nanotechnology for targeted drug delivery.

Gastrointestinal digestive fate of whey protein isolate coated liposomes loading astaxanthin: Lipolysis, release, and bioaccessibility

Whey protein isolate coated astaxanthin-loaded liposomes were prepared in this work. The gastrointestinal digestive fate of whey protein isolate coated astaxanthin-loaded liposomes was evaluated in terms of particle size, size distribution, zeta potential, and morphology during in vitro digestion as a function of time. Analysis on the particle size and morphology of whey protein isolate coated astaxanthin-loaded liposomes showed that the majority of particles maintained spherical shape with a progressive increase of particle size after passage through the digestion. The zeta potential on whey protein isolate coated astaxanthin-loaded liposomes became highly negative after digestion. As compared in uncoated liposomes, the astaxanthin release in whey protein isolate coated liposomes was slower in simulated gastric fluid digestion, while was faster in simulated intestinal fluid digestion. Through in vitro digestion, the bioaccessibility of astaxanthin was improved significantly after whey protein isolate coating. It was also found that the whey protein isolate coating could protect liposomes against destruction and suppress the lateral mobility of pyrene, resulting in lower micropolarity and fluidity of liposomal membrane during the digestion. These findings may guide the potential application of whey protein isolate coated liposomes for improving the bioaccessibility and stability of astaxanthin in nutraceuticals and pharmaceutics. • The digestion behavior of whey protein isolate coated astaxanthin-loaded liposomes. • Astaxanthin-loaded liposomes after coating were stable under gastric conditions. • The bioaccessibility of astaxanthin was improved. • Whey protein isolate coating could protect liposomes during the digestion.

Insight into dual fluorescence effects induced by molecular aggregation occurring in membrane model systems containing 1,3,4-thiadiazole derivatives

This work reports on biophysical insights into the excited state intramolecular proton transfer (ESIPT) processes taking place in three 1,3,4-thiadiazole derivatives that served as model compounds, on which electronic absorption, fluorescence, Fourier-transform infrared spectroscopy (FTIR), surface plasmon resonance (SPR) and electrochemical impedance spectroscopy (EIS) studies were performed. The fluorescence spectra recorded in various solvents revealed an interesting dual fluorescence effect. In molecules in their monomeric form, the effect is associated with the ESIPT phenomenon, and may be further enhanced by aggregation-related effects, such as aggregation-induced emissions. Other spectroscopic studies on the selected molecules in a liposomal medium as a model revealed that, in a biomimetic environment, they can exist in both monomeric and aggregated forms. In both cases, however, the effects observed are closely related to the lipid’s main phase transition temperature and the structure of the molecule. Introduction of specific substituents to the phenyl moiety either allows or prevents proton transfer from occurring in the excited state. The hydrophobicity changes in a lipid environment may result in an emergence of specific molecular forms and therefore either facilitate or hinder ESIPT processes. SPR and EIS confirmed the significant hydrophobicity changes in the model lipid systems, while FTIR measurements revealed a notable influence of 1,3,4-thiadiazoles on the fluidity of liposomal membranes. The results obtained clearly show that the thiadiazole derivatives are very good model molecules for studying hydrophobic-hydrophilic environments, and particularly with polymers or liposomes used as drug delivery systems.

Flotillin-mediated membrane fluidity controls peptidoglycan synthesis and MreB movement.

The bacterial plasma membrane is an important cellular compartment. In recent years it has become obvious that protein complexes and lipids are not uniformly distributed within membranes. Current hypotheses suggest that flotillin proteins are required for the formation of complexes of membrane proteins including cell-wall synthetic proteins. We show here that bacterial flotillins are important factors for membrane fluidity homeostasis. Loss of flotillins leads to a decrease in membrane fluidity that in turn leads to alterations in MreB dynamics and, as a consequence, in peptidoglycan synthesis. These alterations are reverted when membrane fluidity is restored by a chemical fluidizer. In vitro, the addition of a flotillin increases membrane fluidity of liposomes. Our data support a model in which flotillins are required for direct control of membrane fluidity rather than for the formation of protein complexes via direct protein-protein interactions.

Retention of Eucalyptol, a Natural Volatile Insecticide, in Delivery Systems Based on Hydroxypropyl‐β‐Cyclodextrin and Liposomes

AbstractEucalyptol (Euc) is a natural monoterpene with insecticide effects. Being highly volatile and sensitive to ambient conditions, its encapsulation would enlarge its application. Euc‐loaded conventional liposomes (CL), cyclodextrin/drug inclusion complex, and drug‐in‐cyclodextrin‐in‐liposomes (DCL) are prepared to protect Euc from degradation, reduce its evaporation, and provide its controlled release. The liposomal suspension is freeze‐dried using hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) as cryoprotectant. The liposomes are characterized before and after freeze‐drying. The effect of Euc on the fluidity of liposomal membrane is also examined. A release study of Euc from delivery systems, in powder and reconstituted forms, is performed by multiple head extraction at 60 °C after 6 months of storage at 4 °C. CL and DCL suspensions are homogeneous, show nanometric vesicles size, spherical shape, and negative surface charge before and after freeze‐drying. Moreover, HP‐β‐CD does not affect the fluidity of liposomes. CL formulations present a weak encapsulation for Euc. The loading capacity of eucalyptol in DCL is 38 times higher than that in CL formulation. In addition, freeze‐dried DCL and HP‐β‐CD/Euc inclusion complex show a higher retention of eucalyptol than CL delivery system. Both carrier systems HP‐β‐CD/Euc and Euc‐loaded DCL decrease Euc evaporation and improve its retention.Practical Applications: Eucalyptol is a natural insecticide. It is highly volatile and poorly soluble in water. To enlarge its application, its encapsulation in three delivery systems (conventional liposomes, cyclodextrin/drug inclusion complex, combined system composed of cyclodextrin inclusion complex and liposome) is studied. In this paper it is proved that cyclodextrin/eucalyptol inclusion complex and eucalyptol‐in‐cyclodextrin‐in‐liposome are effective delivery systems for encalyptol encapsulation, retention, and release.

Cultivation at high osmotic pressure confers ubiquinone 8–independent protection of respiration on Escherichia coli

Cultivation at high osmotic pressure confers ubiquinone 8–independent protection of respiration on Escherichia coli

Exploring the influence of inhaled liposome membrane fluidity on its interaction with pulmonary physiological barriers.

Liposomes are promising vectors for pulmonary drug delivery, and have been used in marketed inhalation products. Membrane fluidity is an important property of liposomes. However, the influence of liposome membrane fluidity on its interaction with pulmonary physiological barriers is still unclear and needs elucidation. Here, a series of PEGylated DPPC (1,2-dihexadecanoyl-rac-glycero-3-phosphocholine) liposomes with different membrane fluidity were prepared, and their interaction with different pulmonary physiological barriers, including the mucus permeation capacity, macrophage uptake, trachea distribution and retention behavior, was investigated. The liposomes exhibited sizes of around 100 nm, near-neutral surface charge, and the membrane fluidity increased with increasing cholesterol ratio. In vitro studies showed that the liposomes with lower membrane fluidity presented optimal mucus permeation efficiency, while those with higher membrane fluidity displayed lower macrophage uptake. An in vivo trachea distribution study revealed that liposomes with low or medium membrane fluidity exhibited enhanced trachea permeation. No significant difference in lung retention was found among these liposomes. In conclusion, the mucus permeation and macrophage phagocytosis behavior of liposomes could be well tuned by changing their membrane fluidity.

Cultivation at high osmotic pressure confers ubiquinone 8-independent protection of respiration on Escherichia coli.

Ubiquinone 8 (coenzyme Q8 or Q8) mediates electron transfer within the aerobic respiratory chain, mitigates oxidative stress, and contributes to gene expression in Escherichia coli In addition, Q8 was proposed to confer bacterial osmotolerance by accumulating during growth at high osmotic pressure and altering membrane stability. The osmolyte trehalose and membrane lipid cardiolipin accumulate in E. coli cells cultivated at high osmotic pressure. Here, Q8 deficiency impaired E. coli growth at low osmotic pressure and rendered growth osmotically sensitive. The Q8 deficiency impeded cellular O2 uptake and also inhibited the activities of two proton symporters, the osmosensing transporter ProP and the lactose transporter LacY. Q8 supplementation decreased membrane fluidity in liposomes, but did not affect ProP activity in proteoliposomes, which is respiration-independent. Liposomes and proteoliposomes prepared with E. coli lipids were used for these experiments. Similar oxygen uptake rates were observed for bacteria cultivated at low and high osmotic pressures. In contrast, respiration was dramatically inhibited when bacteria grown at the same low osmotic pressure were shifted to high osmotic pressure. Thus, respiration was restored during prolonged growth of E. coli at high osmotic pressure. Of note, bacteria cultivated at low and high osmotic pressures had similar Q8 concentrations. The protection of respiration was neither diminished by cardiolipin deficiency nor conferred by trehalose overproduction during growth at low osmotic pressure, but rather might be achieved by Q8-independent respiratory chain remodeling. We conclude that osmotolerance is conferred through Q8-independent protection of respiration, not by altering physical properties of the membrane.

Preparation and Characterization of PEGylated C18 Fatty Acids/Anti-SNAP25 Antibody-Targeted Liposomes

Background:Unsaturated C18 fatty acids, such as oleic acid (L1), linoleic acid (L2), and linolenic acid (L3), are a good choice of lipids to prepare liposomes. They are inexpensive, biocompatible, nontoxic, and readily available compared with phospholipids. Moreover, cis-double bonds of unsaturated fatty acids prevent the packing of molecules which increases membrane fluidity in liposomes making them a good choice of starting materials to prepare liposomes.Objective:Unsaturated C18 fatty acid liposomes, as well as their PEGylated and non- PEGylated antibody-targeted liposomes, were prepared and characterized.Methods:The particle size and zeta potential of the prepared liposomes (1 mM, pH = 7.4) for 28 and 14 days, respectively, were monitored and characterized. Membrane-bound antibodies Anti-SNAP25 (AS25) and DOPE PEG2000 (DP) were conjugated to pure C18 fatty acid liposomes to achieve stable fatty acid formulations.Results:The mean particle sizes of pure L1, L2, and L3 liposome solutions were 125, 129, and 122 nm respectively, while their polydispersity index values were 0.28, 0.21, and 0.40 respectively. A large negative zeta potential value of 45 mV was observed due to anionic carboxylate head-group of pure liposomes. The incorporation of AS25 into L1/DP, L2/DP, and L3/DP liposome solutions stabilized their mean particle size and zeta potential measurements over 28 and 14 days, respectively.Conclusion:L1/DP/AS25 was found to be the most stable PEGylated antibody-targeted liposome system because its particle size remained between 90 and 125 nm in 28 days. Transmission electron microscopy observations also supported the incorporation of AS25 and DP on the membrane surface as predicted.

Effects of Capsaicin on Biomimetic Membranes.

Capsaicin is a natural compound that produces a warm sensation and is known for its remarkable medicinal properties. Understanding the interaction between capsaicin with lipid membranes is essential to clarify the molecular mechanisms behind its pharmacological and biological effects. In this study, we investigated the effect of capsaicin on thermoresponsiveness, fluidity, and phase separation of liposomal membranes. Liposomal membranes are a bioinspired technology that can be exploited to understand biological mechanisms. We have shown that by increasing thermo-induced membrane excess area, capsaicin promoted membrane fluctuation. The effect of capsaicin on membrane fluidity was dependent on lipid composition. Capsaicin increased fluidity of (1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) membranes, while it rigidified DOPC and cholesterol-based liposomes. In addition, capsaicin tended to decrease phase separation of heterogeneous liposomes, inducing homogeneity. We imagine this lipid re-organization to be associated with the physiological warming sensation upon consumption of capsaicin. Since capsaicin has been reported to have biological properties such as antimicrobial and as antiplatelet, the results will help unravel these biological properties.