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《Biochimica et Biophysica Acta (BBA)/General Subjects》2020,1864(11):129671
BackgroundThe use of functionalized iron oxide nanoparticles of various chemical properties and architectures offers a new promising direction in theranostic applications. The increasing applications of nanoparticles in medicine require that these engineered nanomaterials will contact human cells without damaging essential tissues. Thus, efficient delivery must be achieved, while minimizing cytotoxicity during passage through cell membranes to reach intracellular target compartments.MethodsDifferential Scanning Calorimetry (DSC), molecular modeling, and atomistic Molecular Dynamics (MD) simulations were performed for two magnetite nanoparticles coated with polyvinyl alcohol (PVA) and polyarabic acid (ARA) in order to assess their interactions with model DPPC membranes.ResultsDSC experiments showed that both nanoparticles interact strongly with DPPC lipid head groups, albeit to a different degree, which was further confirmed and quantified by MD simulations. The two systems were simulated, and dynamical and structural properties were monitored. A bimodal diffusion was observed for both nanoparticles, representing the diffusion in the water phase and in the proximity of the lipid bilayer. Nanoparticles did not enter the bilayer, but caused ordering of the head groups and reduced the area per lipid compared to the pure bilayer, with MAG-PVA interacting more strongly and being closer to the lipid bilayer.ConclusionsResults of DSC experiments and MD simulations were in excellent agreement. Our findings demonstrate that the external coating is a key factor that affects nanoparticle-membrane interactions. Magnetite nanoparticles coated with PVA and ARA did not destabilize the model membrane and can be considered promising platforms for biomedical applications.General significanceUnderstanding the physico-chemical interactions of different nanoparticle coatings in contact with model cell membranes is the first step for assessing toxic response and could lead to predictive models for estimating toxicity. DSC in combination with MD simulations is an effective strategy to assess physico-chemical interactions of coated nanoparticles with lipid bilayers. 相似文献
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The effects of (-)-delta 8-tetrahydrocannabinol (delta 8-THC) and its biologically inactive O-methyl ether analog on model phospholipid membranes were studied using a combination of differential scanning calorimetry (DSC), small angle X-ray diffraction and solid state 2H-NMR. The focus of this work is on the amphipathic interactions of cannabinoids with membranes and the role of the free phenolic hydroxyl group which is the only structural difference between these two cannabinoids. Identically prepared aqueous multilamellar dispersions of phosphatidylcholines in the absence and presence of cannabinoids were used. The DSC thermograms and X-ray diffraction patterns of these preparations allowed us to detect the strikingly different manners in which these two cannabinoids affect the thermotropic properties and the thickness of the bilayer. In order study the effects of the cannabinoids on different regions of the bilayer, we used solid state 2H-NMR with four sets of model membranes from dipalmitoylphosphatidylcholine deuterated in different sites, viz., the choline trimethylammonium head group, or one of the following three groups in the acyl chains; the 2'-methylene, 7'-methylene, 16'-methyl groups. Analysis of quadrupolar splittings indicated that delta 8-THC resides near the bilayer interface and the inactive analog sinks deeper towards the hydrophobic region. The temperature dependence of the solid state 2H-NMR spectra showed that, during the bilayer phase transition, the disordering of the choline head groups is a separate event from the melting of the acyl chains, and that amphipathic interactions between delta 8-THC and the membrane separate these two events further apart in temperature. The inactive analog lacks the ability to induce such a perturbation. 相似文献
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A group of circular dichroism (CD) active phospholipids has been synthesised, in which one or both acyl chains has been replaced with a cinnamoyl or azobenzene chromophore-containing acid. Studies on the structure, CD activity and thermodynamic property of liposome membranes composed of CD active phospholipids were carried out. CD active liposomes were found to be stable, normal liposomes of approximately 550 A diameter based on the electron micrograph and dynamic light scattering, and to have thermodynamic property similar to the conventional phospholipid membranes without serious perturbation by aromatic bulk groups based on DSC. Liposomes composed of phospholipid having two trans-azobenzene chromophores showed an extremely large CD enhancement even well above Tc. This CD enhancement was drastically changed by the presence of cis-azobenzene chromophore and cis-cis isomer content after irradiation was higher than the theoretical value, suggesting the importance of interchromophore interaction in the liposome membranes. 相似文献
5.
《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》2001,750(1):51-60
Unilamellar liposomes with entrapped fluorescent dye calcein were stably immobilized in gel beads by avidin–biotin-binding. The immobilized liposomes remained extremely stable upon storage and chromatographic runs. The immobilized calcein-entrapped liposomes were utilized for fluorescent analysis of solute–membrane interactions, which in some cases are too weak to be detected by chromatographic retardation. A liposome column was used as a sensitive probe to detect the interactions of membranes with pharmaceutical drugs, peptides and proteins. Retardation of the solutes was monitored using a UV detector. Perturbation of the membranes, reflected as leakage of the entrapped calcein by some of the solutes, can thus be detected on-line using a flow-fluorescent detector. For the amphiphilic drugs or synthetic peptides, perturbation of membranes became more pronounced when the retardation (hydrophobicity) of the molecules increased. On the other hand, in the case of positively-charged peptides, polylysine, or partially denatured bovine carbonic anhydrase, significant dye leakage from the liposomes was observed although the retardation was hardly to be measured. Weak protein–membrane interactions can thus be assumed from the large leakage of calcein from the liposomes. This provides additional useful information for solute–membrane interactions, as perturbation of the membranes was also indicated by avidin–biotin-immobilized liposome chromatography (ILC). 相似文献
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Chlorinated hydrocarbons, such as the pesticide lindane (gamma-hexachlorocyclohexane), quench the fluorescence of carbazole. The observed quenching is a result of the molecular contacts which occur upon diffusional collisions. Because the amount of quenching depends upon the collisional frequency between carbazole and pesticide, this phenomenon provides a measure of both the diffusional rate of lindane and its local concentration. The carbazole fluorophore is localized within phosphatidylcholine bilayers by cosonicating the lipid with a newly synthesized phospholipid, beta-(11-(9-carbazole)-undecanoyl)-L-alpha-phosphatidylcholine. Using this probe in dimyristoyl-L-alpha-phosphatidylcholine vesicles, and the above mentioned quenching phenomena, we determined the lindane diffusion rate within the bilayer to be 5.7.10-7 cm2/s at 37 degrees C. Measurement of the apparent quenching constant at various dimyristoyl phosphatidylcholine concentrations yielded a lipid-water partition coefficient for lindane of 9500, which is in agreement with the value of 8980 obtained by our equilibrium dialysis experiments. Vesicles of dimyristoyl-L-alpha-phosphatidylcholine become saturated with lindane at a pesticide to lipid molar ratio of approx. 0.28. These results demonstrate the possibility of using the quenching of carbazole fluorescence to investigate the transport and partitioning of pesticides within biological membranes. This ability should prove useful in studies of the interactions of chlorinated hydrocarbons with cell membranes. 相似文献
7.
Swapnil A. Malekar Ashish L. Sarode Alvin C. BachII David R. Worthen 《AAPS PharmSciTech》2016,17(6):1468-1476
The interactions with and effects of five chemically distinct, bioactive phenolic compounds on the lipid bilayers of model dipalmitoylphosphatidylcholine (DPPC) liposomes were investigated. Complementary analytical techniques, including differential scanning calorimetry (DSC) and phosphorus and proton nuclear magnetic resonance spectroscopy (NMR), were employed in order to determine the location of the compounds within the bilayer and to correlate location with their effects on bilayer characteristics and liposomal stability. As compared to the phenolic compounds localized in the glycerol region of the DPPC head group within the bilayer, which enhanced the colloidal stability of the liposomes, compounds located closer to the center of the bilayer reduced vesicle stability as a function of time. Molecules present in the upper region of liposomal DPPC acyl chains (C1–C10) inhibited liposomal aggregation and size increase, perhaps due to tighter packing of adjoining DPPC molecules and increased surface exposure of DPPC phosphate head groups. These data may be useful for designing liposomal systems containing hydrophobic phenols and other small molecules, selecting appropriate analytical methods for determining their location within liposomal bilayers, and predicting their effects on liposome characteristics early in the liposome formulation development process. 相似文献
8.
A fluorescence quenching method was developed for determining partition coefficients and diffusional rates of small molecules in cell membranes. This method involves quenching the fluorescence of carbazole-labeled membranes by hydrophobic molecules that partition into membranes. Cell membrane phospholipids of mouse LM cells in tissue culture were biosynthetically labeled with the carbazole moiety by supplementing the growth media with 11-(9-carbazolyl)undecanoic acid. Plasma membranes, microsomes, and mitochondria were isolated free of nonmembranous neutral lipids, and the incorporation of the fluorescent probe was characterized. Quenching studies of the carbazole moiety by a series of N-substituted picolinium perchlorate salts showed that the carbazole moiety was located in the hydrophobic interior of the membrane bilayer. The carbazole fluorescence also was quenched by the hydrophobic quenchers lindane, methoxychlor, and 1,1-dichloro-2,2-bis(rho-chlorophenyl)ethylene, indicating that these compounds partitioned into the membrane. Stern-Volmer quenching constants determined by fluorescence lifetime and intensity measurements were identical, as expected for dynamic quenching. The effects of different lipid compositions on quenching constants and partition coefficients were determined by comparing different membrane fractions. These parameters also were measured in membranes from cells in which the phospholipid composition was altered by substituting ethanolamine for choline in the growth medium. Changes in the lipid composition produced changes in the bimolecular quenching constants. For example, bimolecular quenching constants for 1,1-dichloro-2,2-bis(rho-chlorophenyl)ethylene were higher in mitochondrial membranes than in plasma membranes and microsomes. They were also higher in dispersions made from membrane phospholipids as compared with intact membranes or total lipid dispersion.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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The bifunctional Bordetella adenylate cyclase toxin-hemolysin (ACT) penetrates target cell membranes, forms cation-selective channels and subverts cellular signaling by catalyzing uncontrolled conversion of ATP to cAMP. While primarily targeting phagocytes expressing the alphaMbeta2 integrin (CD11b/CD18), the toxin can also penetrate mammalian erythrocytes lacking the receptor and membrane endocytosis. We sought here to analyze the membrane interactions of ACT in a liposome model. Insertion of ACT into liposome membranes required calcium and caused leakage of entrapped fluorescent probes due to liposome disruption, as indicated by similar release kinetics for the approximately 398 Da FITC probe and its approximately 4400 Da dextran conjugate. However, the non-acylated proACT, which does not penetrate cellular membranes, exhibited higher capacity to bind and lyze liposomes than the mature toxin, showing that the fatty-acyl modification was not required for penetration of ACT into the lipid bilayer. Individual deletions within the channel-forming, acylation and repeat domains of ACT abolished its capacity to disrupt both liposomes and erythrocytes. In contrast to erythrocyte binding, however, the liposome binding was only lost upon a simultaneous deletion of both the channel-forming and acylation domains, suggesting that the acylation domain was also involved in liposome penetration of ACT. Moreover, substitutions of glutamates 509 and 516 by lysines, which strongly enhanced the channel-forming and hemolytic activity of ACT, did not affect its capacity to disrupt liposomes. This shows that the mechanism of ACT action in cellular membranes is not fully reproduced in liposome membranes. 相似文献
10.
In recognition of the need to understand better the interactions of the chlorinated hydrocarbon insecticides with cell membranes we investigated the use of fluorescence quenching of membrane-bound fluorophores by these chlorinated hydrocarbons. An extensive survey of potential fluorophores identified the N-alkyl derivatives of carbazole as being especially suitable fluorophores. The fluorescence emission of these derivatives is quenched by a wide variety of commonly-used chlorinated hydrocarbons. This quenching is collisional and does not result in significant photodecomposition.Four structurally distinct carbazole-labeled phospholipids were synthesized, and their structures were confirmed by 270 MHz proton NMR and by chromatographic and chemical means. The carbazole moiety of each labeled phospholipid should be localized at a different depth in lipid bilayer. However, water soluble quenchers indicate that the fluorophores are inaccessible to the aqueous phase, irrespective of their point of attachment to the phospholipids.When incorporated into lipid bilayers, the fluorescence lifetime of these carbazole-labeled phospholipids reveals the collisional frequency between the fluorophore and the chlorinated hydrocarbon. As a result quenching of membrane-bound fluorophores may be used to measure: (1) the diffusional rate of the chlorinated hydrocarbon in the bilayer; (2) the lipid-water partition coefficient; (3) the maximum binding capacity of the membrane for the chlorinated hydrocarbon. Examples of all these measurements are given, and the fluorometric results are confirmed by direct chemical analysis. 相似文献
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We used differential scanning calorimetry (DSC) and electron spin resonance (ESR) spectroscopy to investigate the interactions of Losartan, a potent, orally active Angiotensin II AT(1) receptor antagonist with phospholipid membranes. DSC results showed that Losartan sensitively affected the chain-melting behavior of dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) bilayer membranes. ESR spectroscopy showed that phosphatidylcholines spin-labeled at the 5-position of the sn-2 acyl chain (n-PCSL with n=5), incorporated either in DMPC or DPPC bilayers containing Losartan, were restricted in motion both in the gel and in the liquid-crystalline membrane phases, indicating a location of the antagonist close to the interfacial region of the phosphatidylcholine bilayer. At high drug concentrations (mole fraction >/= x=0.60), the decrease in chain mobility registered by 5-PCSL in fluid-phase membranes is smaller than that found at lower concentrations, whereas that registered by 14-PCSL is further increased. This indicates a different mode of interaction with Losartan at high concentrations, possibly arising from a location deeper within the bilayer. Additionally, Losartan reduced the spin-spin broadening of 12-PCSL spin labels in the gel-phase of DMPC and DPPC bilayers. As a conclusion, our study has shown that Losartan interacts with phospholipid membranes by affecting both their thermotropic behavior and molecular mobility. 相似文献
12.
Wrobel D Kłys A Ionov M Vitovic P Waczulikowa I Hianik T Gomez-Ramirez R de la Mata J Klajnert B Bryszewska M 《Chemistry and physics of lipids》2012,165(4):401-407
The aim of this work was to study interactions between cationic carbosilane dendrimers (CBS) and lipid bilayers or monolayers. Two kinds of second generation carbosilane dendrimers were used: NN16 with Si-O bonds and BDBR0011 with Si-C bonds. The results show that cationic carbosilane dendrimers interact both with liposomes and lipid monolayers. Interactions were stronger for negatively charged membranes and high concentration of dendrimers. In liposomes interactions were studied by measuring fluorescence anisotropy changes of fluorescent labels incorporated into the bilayer. An increase in fluorescence anisotropy was observed for both fluorescent probes when dendrimers were added to lipids that means the decreased membrane fluidity. Both the hydrophobic and hydrophilic parts of liposome bilayers became more rigid. This may be due to dendrimers' incorporation into liposome bilayer. For higher concentrations of both dendrimers precipitation occurred in negatively charged liposomes. NN16 dendrimer interacted stronger with hydrophilic part of bilayers whereas BDBR0011 greatly modified the hydrophobic area. Monolayers method brought similar results. Both dendrimers influenced lipid monolayers and changed surface pressure. For negatively charged lipids the monitored parameter changed stronger than for uncharged DMPC lipids. Moreover, NN16 dendrimer interacted stronger than the BDBR0011. 相似文献
13.
Satchell DP Sheynis T Shirafuji Y Kolusheva S Ouellette AJ Jelinek R 《The Journal of biological chemistry》2003,278(16):13838-13846
The bactericidal activity of mouse alpha-defensins (cryptdins) requires proteolytic activation of inactive precursors by matrix metalloproteinase-7 (matrilysin, EC, MMP-7(a)). To investigate mechanisms of cryptdin-4 (Crp4) peptide interactions with membrane bilayers and to determine whether MMP-7-mediated proteolysis activates the membrane disruptive activity of Crp4, associations of Crp4 and melittin with biomimetic lipid/polydiacetylene chromatic vesicles were characterized. The peptides differ in their sensitivity to vesicle lipid composition and their depth of bilayer penetration. Crp4 undergoes strong interfacial binding onto lipid bilayers with disruption of the bilayer head group region, unlike melittin, which inserts more deeply into the hydrophobic core of the bilayer. Colorimetric and tryptophan fluorescence studies showed that Crp4 insertion is favored by negatively charged phospholipids and that zwitterionic and Escherichia coli phospholipids promote stronger interfacial binding; melittin-membrane interactions were independent of either variable. In contrast to the membrane disruptive activity of Crp4, pro-Crp4 did not perturb vesicular membranes, consistent with the lack of bactericidal activity of the precursor, and incubation of Crp4 with prosegment in trans blocked Crp4 and G1W-Crp4 membrane interactions at concentrations that inhibit Crp4 bactericidal activity. CD measurements showed that Crp4 has an expected beta-sheet structure that is not evident in the pro-Crp4 CD trace or when Crp4 is incubated with prosegment, indicating that the beta-sheet signal is attenuated by proregion interactions or possibly disrupted by the prosegment. Collectively, the results suggest that the prosegment inhibits Crp4 bactericidal activity by blocking peptide-mediated perturbation of target cell membranes, a constraint that is relieved when MMP-7 cleaves the prosegment. 相似文献
14.
David I. Fernandez Anton P. Le Brun Tzong-Hsien Lee Paramjit Bansal Marie-Isabel Aguilar Michael James Frances Separovic 《European biophysics journal : EBJ》2013,42(1):47-59
The interactions of the antimicrobial peptide maculatin 1.1 (GLFGVLAKVAAHVVPAIAEHF-NH2) with model phospholipid membranes were studied by use of dual polarisation interferometry and neutron reflectometry and dimyristoylphosphatidylcholine (DMPC) and mixed DMPC–dimyristoylphosphatidylglycerol (DMPG)-supported lipid bilayers chosen to mimic eukaryotic and prokaryotic membranes, respectively. In DMPC bilayers concentration-dependent binding and increasing perturbation of bilayer order by maculatin were observed. By contrast, in mixed DMPC–DMPG bilayers, maculatin interacted more strongly and in a concentration-dependent manner with retention of bilayer lipid order and structure, consistent with pore formation. These results emphasise the importance of membrane charge in mediating antimicrobial peptide activity and emphasise the importance of using complementary methods of analysis in probing the mode of action of antimicrobial peptides. 相似文献
15.
The interactions of serum proteins are diverse, complex and can lead to dramatic effects on liposome stability and in vivo behavior; conversely lipids can modify the biological activities of serum proteins. Serum lipoproteins can potentially destabilize bilayer membranes leading to vesicle disruption and loss of contents; irregularities in the lipid bilayer, such as those which exist at phase boundaries, promote the destabilizing effects of lipoproteins. Other serum components such as fibronectin, immunoglobulins and C reactive protein can modify the biological properties of liposomes by promoting interactions with reticuloendothelial cells and/or activation of the complement system. Liposomes can avidly bind certain serum clotting factors, a process which can lead to dramatic effects on the clotting cascade. Thus the interactions of liposomes with serum proteins can reciprocally effect both components involved. 相似文献
16.
The fusogenic properties of Rz1, the proline-rich lipoprotein that is the bacteriophage lambda Rz1 gene product, were studied. Light scattering was used to monitor Rz1-induced aggregation of artificial neutral (dipalmitoylphosphatidylcholine/cholesterol) and negatively charged (dipalmitoylphosphatidylcholine/cholesterol/dioleoylphosphatidylserin e) liposomes. Fluorescence assays [the resonance energy transfer between N-(7-nitro-2,1,3-benzoxadiazol-4-yl)phosphatidylethanolamine and N-(lissamine rhodamine B sulfonyl)dihexadecanol-sn-glycero-3-phosphoethanolamine lipid fluorescent probes, as well as fluorescent complex formation between terbium ions and dipicolinic acid encapsulated in two liposome populations and calcein fluorescence] were used to monitor Rz1-induced lipid mixing, contents mixing and leakage of neutral and negatively charged liposomes. The results demonstrated that Rz1 caused adhesion of neutral and negatively charged liposomes with concomitant lipid mixing; membrane distortion, leading to the fusion of liposomes and hence their internal content mixing; and local destruction of the membrane accompanied by leakage of the liposome contents. The use of artificial membranes showed that Rz1 induced the fusion of membranes devoid of any proteins. This might mean that the proline stretch of Rz1 allowed interaction with membrane lipids. It is suggested that Rz1-induced liposome fusion was mediated primarily by the generation of local perturbation in the bilayer lipid membrane and to a lesser extent by electrostatic forces. 相似文献
17.
Chlorinated hydrocarbons, such as the pesticide lindane (γ-hexachlorocyclohexane), quench the fluorescence of carbazole. The observed quenching is a result of the molecular contacts which occur upon diffusional collisions. Because the amount of quenching depends upon the collisional frequency between carbazole and pesticide, this phenomenon provides a measure of both the diffusional rate of lindane and its local concentration. The carbazole fluorophore is localized within phosphatidylcholine bilayers by cosonicating the lipid with a newly synthesized phospholipid, β-(11-(9-carbazole)-undecanoyl)-l-α-phosphatidylcholine. Using this probe in dimyristoyl-l-α-phosphatidylcholine vesicles, and the above mentioned quenching phenomena, we determined the lindane diffusion rate within the bilayer to be 5.7 · 10−7cm2/s at 37°C. Measurement of the apparent quenching constant at various dimyristoyl phosphatidylcholine concentrations yielded a lipid-water partition coefficient for lindane of 9500, which is in agreement with the value of 8980 obtained by our equilibrium dialysis experiments. Vesicles of dimyristoyl-l-α-phosphatidylcholine become saturated with lindane at a pesticide to lipid molar ratio of approx. 0.28.These results demonstrate the possibility of using the quenching of carbazole fluorescence to investigate the transport and partitioning of pesticides within biological membranes. This ability should prove useful in studies of the interactions of chlorinated hydrocarbons with cell membranes. 相似文献
18.
Membrane traffic requires the generation of high-curvature lipid-bound transport carriers represented by tubules and vesicles. The mechanisms through which membranes are deformed has gained much recent attention. A major advance has been the demonstration that direct interactions between cytosolic proteins and lipid bilayers are important in the acquisition of membrane curvature. Rather than being driven only by the formation of membrane-associated structural scaffolds, membrane deformation requires physical perturbation of the lipid bilayer. A variety of proteins have been identified that directly bind and deform membranes. An emerging theme in this process is the importance of amphipathic peptides that partially penetrate the lipid bilayer. 相似文献
19.
Alcohol effects on lipid bilayer permeability to protons and potassium: relation to the action of general anesthetics 总被引:1,自引:0,他引:1
Past work has shown that general anesthetics perturb the membranes of isolated synaptic vesicles, thereby increasing permeability to protons and inhibiting the ability of the vesicles to take up catecholamines. It has been proposed that such effects may produce anesthesia through inhibition of synaptic transmission. The mechanisms of perturbation is unknown. Two possible explanations include alterations of dielectric constant or production of defects as anesthetics partition into the bilayer phase. In order to choose between these alternatives, we measured the effect of nine alcohols and two alkanes on liposome permeability to protons and potassium. Ionic permeability was increased by alcohols and alkanes to similar degrees, thereby ruling out direct effects on the membrane dielectric constant caused by partitioning of anesthetics into the bilayer. Other experiments confirmed earlier reports that the enhanced permeability caused by anesthetics is not specific for protons. We conclude that these membrane perturbants act by increasing the number of transient, ion-conducting defects normally present in the bilayer structure. 相似文献
20.
《Biophysical journal》2022,121(8):1512-1524
Antimicrobial peptides are promising therapeutic agents to mitigate the global rise of antibiotic resistance. They generally act by perturbing the bacterial cell membrane and are thus less likely to induce resistance. Because they are membrane-active molecules, it is critical to verify and understand their potential action toward eukaryotic cells to help design effective and safe drugs. In this work, we studied the interaction of two antimicrobial peptides, aurein 1.2 and caerin 1.1, with red blood cell (RBC) membranes using in situ 31P and 2H solid-state NMR (SS-NMR). We established a protocol to integrate up to 25% of deuterated fatty acids in the membranes of ghosts, which are obtained when hemoglobin is removed from RBCs. Fatty acid incorporation and the integrity of the lipid bilayer were confirmed by SS-NMR and fluorescence confocal microscopy. Leakage assays were performed to assess the lytic power of the antimicrobial peptides. The in situ perturbation of the ghost membranes by aurein 1.2 and caerin 1.1 revealed by 31P and 2H SS-NMR is consistent with membrane perturbation through a carpet mechanism for aurein 1.2, whereas caerin 1.1 acts on RBCs via pore formation. These results are compatible with fluorescence microscopy images of the ghosts. The peptides interact with eukaryotic membranes following similar mechanisms that take place in bacteria, highlighting the importance of hydrophobicity when determining such interactions. Our work bridges model membranes and in vitro studies and provides an analytical toolbox to assess drug toxicity toward eukaryotic cells. 相似文献