Bilayer Thickness Research Articles

Boron Cluster Anions Dissolve En Masse in Lipids Causing Membrane Expansion and Thinning

AbstractBoron clusters are applied in medicinal chemistry because of their high stability in biological environments and intrinsic ability to capture neutrons. However, their intermolecular interactions with lipid membranes, which are critical for their cellular delivery and biocompatibility, have not been comprehensively investigated. In this study, we combine different experimental methods – Langmuir monolayer isotherms at the air–water interface, calorimetry (DSC, ITC), and scattering techniques (DLS, SAXS) – with MD simulations to evaluate the impact of closo‐dodecaborate clusters on model membranes of different lipid composition. The cluster anions interact strongly with zwitterionic membranes (POPC and DPPC) via the chaotropic effect and cause pronounced expansions of lipid monolayers. The resulting lipid membranes contain up to 33 mol % and up to 52 weight % of boron cluster anions even at low aqueous cluster concentrations (1 mM). They show high (μM) affinity to the hydrophilic‐hydrophobic interface, affecting the structuring of the lipid chains, and therefore triggering a sequence of characteristic effects: (i) an expansion of the surface area per lipid, (ii) an increase in membrane fluidity, and (iii) a reduction of bilayer thickness. These results aid the design of boron cluster derivatives as auxiliaries in drug design as well as transmembrane carriers and help rationalize potential toxicity effects.

Boron Cluster Anions Dissolve En Masse in Lipids Causing Membrane Expansion and Thinning.

Boron clusters are applied in medicinal chemistry because of their high stability in biological environments and intrinsic ability to capture neutrons. However, their intermolecular interactions with lipid membranes, which are critical for their cellular delivery and biocompatibility, have not been comprehensively investigated. In this study, we combine different experimental methods - Langmuir monolayer isotherms at the air-water interface, calorimetry (DSC, ITC), and scattering techniques (DLS, SAXS) - with MD simulations to evaluate the impact of closo-dodecaborate clusters on model membranes of different lipid composition. The cluster anions interact strongly with zwitterionic membranes (POPC and DPPC) via the chaotropic effect and cause pronounced expansions of lipid monolayers. The resulting lipid membranes contain up to 33 mol % and up to 52 weight % of boron cluster anions even at low aqueous cluster concentrations (1 mM). They show high (μM) affinity to the hydrophilic-hydrophobic interface, affecting the structuring of the lipid chains, and therefore triggering a sequence of characteristic effects: (i) an expansion of the surface area per lipid, (ii) an increase in membrane fluidity, and (iii) a reduction of bilayer thickness. These results aid the design of boron cluster derivatives as auxiliaries in drug design as well as transmembrane carriers and help rationalize potential toxicity effects.

2D Titanium Carbide MXene and Single-Molecule Fluorescence: Distance-Dependent Nonradiative Energy Transfer and Leaflet-Resolved Dye Sensing in Lipid Bilayers.

Despite their growing popularity, many fundamental properties and applications of MXene materials remain underexplored. Here, the nonradiative energy transfer properties of 2D titanium carbide MXene are investigatedand their application in single-molecule biosensing is explored for the first time. DNA origami positioners are used for single dye placement immobilized by a specific chemistry based on glycine-MXene interactions, allowing precise control of their orientation on the surface. Each DNA origami structure carries a single dye molecule at predetermined heights. Single-molecule fluorescence confocal microscopy reveals that energy transfer of an organic emitter (ATTO 542) on transparent thin films made of spincast Ti3C2Tx flakes follows a cubic distance dependence, where 50% of energy transfer efficiency is reached at 2.7nm (d0). MXenes are applied as short-distance spectroscopic nanorulers, determining z distances of dye-labeled supported lipid bilayers fused on MXene's hydrophilic surface. Hydration layer (2.1nm) and lipid bilayer thickness (4.5nm) values that agree with the literature are obtained. These results highlight titanium carbide MXenes as promising substrates for single-molecule biosensing of ultrathin assemblies, owing to their sensitivity near the interface, a distance regime that is typically inaccessible to other energy transfer tools.

Photocurrent Spectroscopy of Dark Magnetic Excitons in 2D Multiferroic NiI2.

Two-dimensional (2D) antiferromagnetic (AFM) semiconductors are promising components of opto-spintronic devices due to terahertz operation frequencies and minimal interactions with stray fields. However, the lack of net magnetization significantly limits the number of experimental techniques available to study the relationship between magnetic order and semiconducting properties. Here, they demonstrate conditions under which photocurrent spectroscopy can be employed to study many-body magnetic excitons in the 2D AFM semiconductor NiI2. The use of photocurrent spectroscopy enables the detection of optically dark magnetic excitons down to bilayer thickness, revealing a high degree of linear polarization that is coupled to the underlying helical AFM order of NiI2. In addition to probing the coupling between magnetic order and dark excitons, this work provides strong evidence for the multiferroicity of NiI2 down to bilayer thickness, thus demonstrating the utility of photocurrent spectroscopy for revealing subtle opto-spintronic phenomena in the atomically thin limit.

Heterogeneous Morphologies and Hardness of Co-Sputtered Thin Films of Concentrated Cu-Mo-W Alloys.

Heterogeneous microstructures in Cu-Mo-W alloy thin films formed by magnetron co-sputtering immiscible elements with concentrated compositions are characterized using scanning transmission electron microscopy (STEM) and nanoindentation. In this work, we modified the phase separated structure of a Cu-Mo immiscible system by adding W, which impedes surface diffusion during film growth. The heterogeneous microstructures in the Cu-Mo-W ternary system exhibited bicontinuous matrices and agglomerates composed of Mo(W)-rich phase. This is unique, as these are the slower-diffusing species, contrasting past reports of binary Cu-Mo thin films that exhibited Cu-rich agglomerates. The bicontinuous matrices comprised of Cu-rich and Mo(W)-rich phases exhibited bilayer thicknesses of less than 5 nm. The hardness of these thin films measured using nanoindentation is reported and compared to similar multilayers and nanocomposites in binary systems.

Ex vivo electrical bioimpedance measurements and Cole modelling on the porcine colon and rectum

Different pathological changes in the large intestine wall, associated with the development of different chronic diseases, including colorectal cancer, could be reflected in electrical bioimpedance readings. Thickness and composition of the mucus bilayer covering it in the luminal side, abundance of bacteria of the intestinal microbiota, the permeability of the epithelium and inflammation are some of these. However, scientific literature on electrical passive properties of the large intestine is scarce. In this study, complex impedance measurements at 8 frequencies were carried out on 6 specimens of porcine colorectal tissue, within half ab hour post-mortem, obtained from a local abattoir. For 5 different distances, measured proximally from the border of the anus, 3 readings were taken at 3 different points with a tetrapolar probe. The results show 2 different dielectric dispersions in the α and β regions and it seems that there is a relationship between the values of resistivities and the thickness of the wall. Also, parameter values both for the Cole and the geometrical models are given. Another set of electrical bioimpedance readings was carried out in order to assess the effect of the mucus layer on electrical properties of the tissue. It seems that these layers are related to the low frequency dispersion. Finally, electrical passive properties of porcine colorectal tissue, reported in this work, give reference values and behaviour patterns that could be applied for further research in human medicine, based on bioimpedance measurements.

Effect of sputtering power and thickness ratios on the materials properties of Cu–W and Cu–Cr bilayer thin films using high power impulse magnetron and DC magnetron sputtering

This study investigates the influence of Cu thickness ratios on the structural, morphological, and mechanical properties of sputtered Cu–W and Cu–Cr bilayer thin films. Employing high power impulse magnetron sputtering (HiPIMS), five distinct thickness ratios of 1:3, 3:5, 1:1, 5:3, and 3:1 were analyzed and compared to bilayer films developed using direct current magnetron sputtering (DCMS). The microstructural and surface characteristics of these films were evaluated using x-ray diffraction (XRD), atomic force microscopy, and scanning electron microscopy. Electrical properties were measured using a four-point probe, while mechanical properties were assessed through nanoindentation. Results reveal that increasing Cu thickness in Cu–W and Cu–Cr bilayers inversely affects hardness, grain size, and roughness, highlighting the influence of thickness ratios on film properties. Films with a higher Cu thickness ratio in both Cu–W and Cu–Cr bilayer systems deposited by HiPIMS exhibited lower hardness, smaller grain size, and reduced average roughness. Cross-sectional analysis and XRD confirmed the impact of thickness ratio on crystal phase and microstructure, indicating smoother columnar structures. Specifically, the HiPIMS-deposited Cu–Cr 3-1 film exhibited the lowest resistivity, at 4.77 μΩ cm, and hardness, measuring 8.26 GPa. Moreover, the 1:1 ratio films of Cu–W and Cu–Cr demonstrated hardness values of 13.81 and 11.37 GPa, respectively, which were 1.39 times higher than the films grown by DCMS. Additionally, variations in the bilayer thickness ratio significantly affected the electrical properties of the films. The enhanced properties of HiPIMS films are attributed to the higher peak power density of the target, leading to increased ion energy and deposition of dense grain structures.

Thermoresponsive supramolecular nanocontainers from ionic complexes of amphiphilic wedge-shaped mesogens and polybases

Multi-responsive polymeric nanocontainers attract significant attention for their potential applications in biotechnology, drug delivery, catalysis, and other fields. By incorporating a liquid-crystalline (LC) mesogenic ligand with an alkyl tail length ranging from 8–12 carbons, ionically linked to the polymer backbone, we generate vesicles with walls significantly thinner than those of conventional polymersomes, approaching the thickness of a lipid bilayer. These LC vesicles, ranging in size from 50–120 nm, are designed to be mechanically robust due to the alignment of the hydrophilic polymer backbone within the plane of the vesicle wall. Additionally, incorporating a temperature-sensitive block into the polymer structure imparts thermoresponsiveness to the nanocontainers, enhancing their functionality and adaptability for various applications. Ionic complexes of hydrophilic polybases, specifically poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and PDMAEMA-b-PNIPAM (poly(N-isopropylacrylamide)) block copolymers, with amphiphilic wedge-shaped mesogens bearing a sulfonic acid group at the focal point were synthesized. The designed nanocontainers, in the form of either vesicles or nanotubes, exhibit a well-defined wall thickness of 5 nm, dictated by the organization of a smectic LC phase. The constructed coarse-grained models elucidate the mechanism of self-assembly, demonstrating that the balance between the hydrophilicity of the main polymer chain and the hydrophobicity of the wedge-shaped pendant groups determines both the internal and external structure of the vesicles.

Binding and unbinding of flexible surfactant bilayers

We have probed the influence of salt and temperature on the spatial periodicity (d) of the fluid lamellar (Lα) phase formed by two ionic amphiphiles, whose bilayer bending rigidity moduli are widely different. In the case of rigid 1,2-dimyristoyl-3-trimethylammonium-propane (chloride salt) (DMTAP) bilayers, d is found to decrease with increasing salt concentration (Cs) in the solution, in qualitative agreement with the DLVO theory. d depends only very weakly on temperature in this system. On the other hand, in the Lα phase formed by highly flexible didodecyldimethylammonium chloride (DDAC) bilayers, d is not set by the minimum of the DLVO potential over a wide range of Cs, due to inter-bilayer repulsion arising from thermal undulations of the bilayers. An abrupt transformation of this undulation stabilized swollen Lα phase into a collapsed Lα phase, where d is comparable to the bilayer thickness, is observed above a threshold value of Cs. At higher Cs an unbinding transition of the bilayers is observed on heating, where the collapsed Lα phase transforms into a dispersion of spatially uncorrelated bilayers. Our observations are consistent with this transition being first-order.

Enhanced dipole-interaction in Nd-Dy-Fe-Co-B/Fe composite thick stacked trilayer

It is crucial to better understand the magnetization reversal process between soft and hard magnets and to achieve a high maximum energy product in thick composite multilayers. In this study, we find that the exchange interactions dominate in soft–hard-magnetic composite bilayers, while dipole interactions are predominant in soft–hard-magnetic composite trilayers. Based on the first-order reversal curve, magnetization reversal models are developed for both the thick composite bilayer and trilayer. Dipole interactions play an important role in the long range, resulting in higher coercivity and remanence in the thick trilayer. A multilayer in a stacked trilayer structure is achieved, which is composed of thick films with a perpendicular magnetic anisotropy at a thickness of up to 16 μm. The enhanced dipole interactions lead to a remanent polarization of 1 T and a maximum energy product of 22.5 MGOe. This work contributes to the preparation of thick films with a high maximum energy product for applications in magnetic microelectromechanical systems.

Morphological Influence on a Nonionic Bilayer Bending Rigidity and Compression Modulus.

The mechanical properties of multilamellar vesicles and their relevance to soft matter physics and material science are of significant interest. The bending rigidity, κ, and compression modulus, B, of three-dimensional (3D) finite nonspontaneous multilamellar vesicles, formed by a nonionic surfactant, are linked to nanoscale bilayer thickness, δ, estimated via small-angle X-ray scattering, and macroscopic elastic modulus measured through small-amplitude oscillatory shear experiments. κ and B significantly differ from the same system in the two-dimensional (2D) infinite nanostructured planar lamellar phase. Particularly, κ3D was found to be much smaller than κ2D, while an opposite behavior was seen for B. The 2D-to-3D morphology transition occurs under a transient mechanical field, resulting in rheopectic behavior. κ scales quadratically with δ, consistent with bilayer membrane theories, and linearly with vesicle radius in the densely packed state. These findings have implications for understanding and designing soft interfaces due to the influence of bending rigidity on transport properties.

Incorporation of short-chain alcohols into fluid bilayers and its effect on membrane dynamic properties as seen by neutron scattering

In this work, we investigate the effect of concentrated alcoholic solutions (up to 40%w) on extruded 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes using scattering techniques. Extrusion in alcoholic aqueous solutions (methanol, ethanol, or butanol) reduces liposome size, evidenced from the decrease in hydrodynamic radius (RH) obtained from dynamic light scattering. Short-chain alcohols such as ethanol and butanol soften the lipid membranes, as observed by the decrease of the unrelaxed bending modulus (κ̃ ) obtained by neutron spin-echo spectroscopy. Thus, softer membranes are easily ruptured during extrusion, leading to a reduction in vesicle radius corroborated by a reduction in both RH and radius of gyration as seen by dynamic and static light scattering. Moreover, model-free analysis of small-angle neutron scattering (SANS) curves suggests that solvent molecules become incorporated into the lipid membrane. Analysing deviations in the scattering invariant from values predicted by mass balance, we find that the volume fraction of liposomes increases, modifying the scattering length density of the assemblies. By quantifying these changes, we estimate that 12% to 18% of the liposome membrane is composed of solvent molecules (alcohol + water), depending on the type of alcohol and its concentration present in solution, with the exception of glycerol where next to no incorporation was observed. Finally, structural parameters obtained through light scattering and changes in contrast profiles calculated from analysis of the invariant were corroborated through modelling of the SANS curves. Modelling suggests that a reduction of bilayer thickness takes place for liposomes dispersed in ethanolic and butanolic solutions, but not in the presence of methanol or glycerol.

(1-Deoxy)ceramides in bilayers containing sphingomyelin and cholesterol

The discovery of a novel sphingolipid subclass, the (1-deoxy)sphingolipids, which lack the 1-hydroxy group, attracted considerable attention in the last decade, mainly due to their involvement in disease. They differed in their physico-chemical properties from the canonical (or 1-hydroxy) sphingolipids and they were more toxic when accumulated in cells, inducing neurodegeneration and other dysfunctions. (1-Deoxy)ceramides, (1-deoxy)dihydroceramides, and (1- deoxymethyl)dihydroceramides, the latter two containing a saturated sphingoid chain, have been studied in this work using differential scanning calorimetry, confocal fluorescence and atomic force microscopy, to evaluate their behavior in bilayers composed of mixtures of three or four lipids. When compared to canonical ceramides (Cer), a C16:0 (1-deoxy)Cer shows a lower miscibility in mixtures of the kind C16:0 sphingomyelin/cholesterol/XCer, where XCer is any (1-deoxy)ceramide, giving rise to the coexistence of a liquid-ordered phase and a gel phase. The latter resembles, in terms of thermotropic behavior and nanomechanical resistance, the gel phase of the C16:0 sphingomyelin/cholesterol/C16:0 Cer mixture [Busto et al., Biophys. J. 2014, 106, 621–630]. Differences are seen between the various C16:0 XCer under study in terms of nanomechanical resistance, bilayer thickness and bilayer topography. When examined in a more fluid environment (bilayers based on C24:1 SM), segregated gel phases are still present. Probably related to such lateral separation, XCer preserve the capacity for membrane permeation, but their effects are significantly lower than those of canonical ceramides. Moreover, C24:1 XCer show significantly lower membrane permeation capacity than their C16:0 counterparts. The above data may be relevant in the pathogenesis of certain sphingolipid-related diseases, including certain neuropathies, diabetes, and glycogen storage diseases.

The impact of transmembrane peptides on lipid bilayer structure and mechanics: A study of the transmembrane domain of the influenza A virus M2 protein

Transmembrane peptides play important roles in many biological processes by interacting with lipid membranes. This study investigates how the transmembrane domain of the influenza A virus M2 protein, M2TM, affects the structure and mechanics of model lipid bilayers. Atomic force microscopy (AFM) imaging revealed small decreases in bilayer thickness with increasing peptide concentrations. AFM-based force spectroscopy experiments complemented by theoretical model analysis demonstrated significant decreases in bilayer's Young's modulus (E) and lateral area compressibility modulus (KA). This suggests that M2TM disrupts the cohesive interactions between neighboring lipid molecules, leading to a decrease in both the bilayer's resistance to indentation (E) and its ability to resist lateral compression/expansion (KA). The large decreases in bilayer elastic parameters (i.e., E and KA) contrast with small changes in bilayer thickness, implying that bilayer mechanics are not solely dictated by bilayer thickness in the presence of transmembrane peptides. The observed significant reduction in bilayer mechanical properties suggests a softening effect on the bilayer, potentially facilitating membrane curvature generation, a crucial step for M2-mediated viral budding. In parallel, our Raman spectroscopy revealed small but statistically significant changes in hydrocarbon chain vibrational dynamics, indicative of minor disordering in lipid chain conformation. Our findings provide useful insights into the complex interplay between transmembrane peptides and lipid bilayers, highlighting the significance of peptide-lipid interactions in modulating membrane structure, mechanics, and molecular dynamics.

Influence of additional intermediate thick Al layers on the reaction propagation and heat flow of Al/Ni reactive multilayers

This study investigates the effects of sputtering and electron beam evaporation (e‐beam) on the microstructure and reactive properties of Al/Ni reactive multilayers (RML). The intermixing zone, a critical factor influencing reaction kinetics, was characterized using high‐resolution transmission electron microscopy and found to be consistently 3 nm for both fabrication methods. Differential scanning calorimetry revealed that e‐beam samples, with thicker Al layers, exhibited slightly higher total molar enthalpy and maintained high reaction temperatures despite reduced reaction velocities in comparison to sputtered samples. X‐ray diffraction confirmed the formation of both Al3Ni2 and AlNi phases in the e‐beam samples. These findings indicate that while thicker bilayer structures reduce reaction velocity, they keep thermal output and mitigate the impact of intermixing zones, leading to similar total molar enthalpy. This analysis underscores the significance of deposition technique and bilayer thickness in optimizing the performance of Al/Ni RML, offering the possibility to establish different phase formations in thicker RML. It advances the control over the reactive properties of reactive multilayers in their applications, for example reactive bonding.This article is protected by copyright. All rights reserved.

Highly-Aligned All-Fiber Actuator with Asymmetric Photothermal-Humidity Response and Autonomous Perceptivity.

Soft robots adapt to complex environments for autonomous locomotion, manipulation, and perception are attractive for robot-environment interactions. Strategies to reconcile environment-triggered actuation and self-powered sensing responses to different stimuli remain challenging. By tuning the in situ vapor phase solvent exchange effect in continuous electrospinning, an asymmetric highly-aligned all-fiber membrane (HAFM) with a hierarchical "grape-like" nanosphere-assembled microfiber structure (specific surface area of 13.6m2g-1) and excellent mechanical toughness (tensile stress of 5.5MPa, and fracture toughness of 798KJm-3) is developed, which shows efficient asymmetric actuation to both photothermal and humidity stimuli. The HAFM consists of a metal-organic framework (MOF)-enhanced moisture-responsive layer and an MXene-improved photothermal-responsive layer, which achieves substantial actuation with a bending curvature up to ≈7.23cm-1 and a fast response of 0.60cm-1s-1. By tailoring the fiber alignment and bi-layer thickness ratio, different types of micromanipulators, automatic walking robots, and plant robots with programmable structures are demonstrated, which are realized for self-powered information perception of material type, object moisture, and temperature by integrating the autonomous triboelectric effect induced by photothermal-moisture actuation. This work presents fiber materials with programable hierarchical asymmetries and inspires a common strategy for self-powered organism-interface robots to interact with complex environments.

Softening in Two-Component Lipid Mixtures by Spontaneous Curvature Variance.

The bending modulus of a lipid bilayer quantifies its mechanical resistance to curvature. It is typically understood in terms of thickness; e.g., thicker bilayers are usually stiffer. Here, we describe an additional and powerful molecular determinant of stiffness─the variance in the distribution of curvature sensitivity of lipids and lipid conformations. Zwitterionic choline and ethanolamine headgroups of glycerophospholipids dynamically explore inter- and intraspecies interactions, leading to transient clustering. We demonstrate that these clusters couple strongly to negative curvature, exciting undulatory membrane modes and reducing the apparent bending modulus. Three force fields (Martini 2, Martini 3, and all-atom CHARMM C36) each show the effect to a different extent, with the coarse-grained Martini models showing the most clustering and thus the most softening. The theory is a guide to understanding the stiffness of biological membranes with their complex composition, as well as how choices of force field parameterization are translated into mechanical stiffness.

Computational analysis of the simultaneous application of ultrasound and electric fields in a lipid bilayer

The combined application of electric fields and ultrasonic waves has shown promise in controlling cell membrane permeability, potentially resulting in synergistic effects that can be explored in the biotechnology industry. However, further clarification on how these processes interact is still needed. The objective of the present study was to investigate the atomic-scale effects of these processes on a DPPC lipid bilayer using molecular dynamics simulations. For higher electric fields, capable of independently forming pores, the application of an ultrasonic wave in the absence of cavitation yielded no additional effects on pore formation. However, for lower electric fields, the reduction in bilayer thickness induced by the shock wave catalyzed the electroporation process, effectively shortening the mean path that water molecules must traverse to form pores. When cavitation was considered, synergistic effects were evident only if the wave alone was able to generate pores through the formation of a water nanojet. In these cases, sonoporation acted as a mean to focus the electroporation effects on the initial pore formed by the nanojet. This study contributes to a better understanding of the synergy between electric fields and ultrasonic waves and to an optimal selection of processing parameters in practical applications of these processes.

Partitioning into ER membrane microdomains impacts autophagic protein turnover during cellular aging

Eukaryotic membranes are compartmentalized into distinct micro- and nanodomains that rearrange dynamically in response to external and internal cues. This lateral heterogeneity of the lipid bilayer and associated clustering of distinct membrane proteins contribute to the spatial organization of numerous cellular processes. Here, we show that membrane microdomains within the endoplasmic reticulum (ER) of yeast cells are reorganized during metabolic reprogramming and aging. Using biosensors with varying transmembrane domain length to map lipid bilayer thickness, we demonstrate that in young cells, microdomains of increased thickness mainly exist within the nuclear ER, while progressing cellular age drives the formation of numerous microdomains specifically in the cortical ER. Partitioning of biosensors with long transmembrane domains into these microdomains increased protein stability and prevented autophagic removal. In contrast, reporters with short transmembrane domains progressively accumulated at the membrane contact site between the nuclear ER and the vacuole, the so-called nucleus-vacuole junction (NVJ), and were subjected to turnover via selective microautophagy occurring specifically at these sites. Reporters with long transmembrane domains were excluded from the NVJ. Our data reveal age-dependent rearrangement of the lateral organization of the ER and establish transmembrane domain length as a determinant of membrane contact site localization and autophagic degradation.

Cryptotanshinone-Induced Permeabilization of Model Phospholipid Membranes: A Biophysical Study.

The Danshen terpenoid cryptotanshinone (CPT) is gaining enormous interest in light of its various outstanding biological activities. Among those, CPT has been shown to interact with cell membranes and, for instance, to have antibacterial activity. Several works have shown that CPT alone, or in combination with other drugs, can effectively act as an antibiotic against various infectious bacteria. Some authors have related the mechanism underlying this action to CPT-membrane interaction. This work shows that CPT readily partitions into phosphatidylcholine membranes, but there is a limiting capacity of accommodation of ca. 1 mol CPT to 3 mol phospholipid. The addition of CPT to unilamellar liposomes composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) causes membrane permeabilization, as shown by fluorescent probe leakage. This process has been kinetically studied, as well as its modulation by incorporation of phosphatidylethanolamine or phosphatidylglycerol, as a model for pathogenic cell membranes. The thermotropic behavior of 1,2-dimyristoylphosphatidylcholine (DMPC) model membranes is weakly affected by CPT, but the terpenoid causes significant dehydration of the polar region of the bilayer and weak disordering of the acyl chain palisade, as observed in Fourier-transform infrared spectroscopy (FTIR) results. Small-angle X-ray scattering (SAXS) shows that CPT increases DMPC bilayer thickness, which could be due to localization near the phospholipid/water interface. Molecular dynamics (MD) simulations show that the lateral diffusion coefficient of the phospholipid increases with the presence of CPT. CPT extends from the polar head region to the center of the bilayer, being centered between the carbonyl groups and the unsaturated region of the POPC, where there is greater overlap. Interestingly, the free energy profiles of a water molecule crossing the lipid membrane show that the POPC membrane becomes more permeable in the presence of CPT. In summary, our results show that CPT perturbs the physicochemical properties of the phospholipid membrane and compromises its barrier function, which could be of relevance to explain part of its antimicrobial or anticancer activities.