Amphiphilic nanoparticles generate curvature in lipid membranes and shape liposome-liposome interfaces.
Ontology highlight
ABSTRACT:
SUBMITTER: Lavagna E
PROVIDER: S-EPMC8530203 | biostudies-literature | 2021 Oct
REPOSITORIES: biostudies-literature
Publications
Amphiphilic nanoparticles generate curvature in lipid membranes and shape liposome-liposome interfaces.
Lavagna E E Güven Z P ZP Bochicchio D D Olgiati F F Stellacci F F Rossi G G
Nanoscale 20211021 40
We show by molecular dynamics that amphiphilic Au nanoparticles (NP) with a diameter of 4 nm generate curvature in phosphatidylcholine lipid membranes. NPs generate negative curvature when they adsorb on the membrane surface but, as they get spontaneously and progressively embedded into the membrane core, the curvature turns positive. As membrane embedding is kinetically slow, both configurations can be observed by Cryo-EM. NP-induced curvature explains the peculiar structure of liposome-liposom ...[more]
Similar Datasets
Project description:Lipid membrane fusion is an essential process for a number of critical biological functions. The overall process is thermodynamically favorable but faces multiple kinetic barriers along the way. Inspired by nature's engineered proteins such as SNAP receptor [soluble N-ethylmale-imide-sensitive factor-attachment protein receptor (SNARE)] complexes or viral fusogenic proteins that actively promote the development of membrane proximity, nucleation of a stalk, and triggered expansion of the fusion pore, here we introduce a synthetic fusogen that can modulate membrane fusion and equivalently prime lipid membranes for calcium-triggered fusion. Our fusogen consists of a gold nanoparticle functionalized with an amphiphilic monolayer of alkanethiol ligands that had previously been shown to fuse with lipid bilayers. While previous efforts to develop synthetic fusogens have only replicated the initial steps of the fusion cascade, we use molecular simulations and complementary experimental techniques to demonstrate that these nanoparticles can induce the formation of a lipid stalk and also drive its expansion into a fusion pore upon the addition of excess calcium. These results have important implications in general understanding of stimuli-triggered fusion and the development of synthetic fusogens for biomedical applications.
| S-EPMC7414053 | biostudies-literature
Project description:The development of synthetic nanomaterials that could embed within, penetrate, or induce fusion between membranes without permanent disruption would have great significance for biomedical applications. Here we describe structure-function relationships of highly water-soluble gold nanoparticles comprised of an ∼1.5-5 nm diameter metal core coated by an amphiphilic organic ligand shell, which exhibit membrane embedding and fusion activity mediated by the surface ligands. Using an environment-sensitive dye anchored within the ligand shell as a sensor of membrane embedding, we demonstrate that particles with core sizes of ∼2-3 nm are capable of embedding within and penetrating fluid bilayers. At the nanoscale, these particles also promote spontaneous fusion of liposomes or spontaneously embed within intact liposomal vesicles. These studies provide nanoparticle design and selection principles that could be used in drug delivery applications, as membrane stains, or for the creation of novel organic/inorganic nanomaterial self-assemblies.
| S-EPMC6311100 | biostudies-literature
Project description:Plasma membranes represent pharmacokinetic barriers for the passive transport of site-specific drugs within cells. When engineered nanoparticles (NPs) are considered as transmembrane drug carriers, the plasma membrane composition can affect passive NP internalization in many ways. Among these, cholesterol-regulated membrane fluidity is probably one of the most biologically relevant. Herein, we consider small (2-5 nm in core diameter) amphiphilic gold NPs capable of spontaneously and nondisruptively entering the lipid bilayer of plasma membranes. We study their incorporation into model 1,2-dioleoyl-sn-glycero-3-phosphocholine membranes with increasing cholesterol content. We combine dissipative quartz crystal microbalance experiments, atomic force microscopy, and molecular dynamics simulations to show that membrane cholesterol, at biologically relevant concentrations, hinders the molecular mechanism for passive NP penetration within fluid bilayers, resulting in a dramatic reduction in the amount of NP incorporated.
| S-EPMC8436204 | biostudies-literature
Project description:We have created FtsZ-YFP-mts where an amphipathic helix on the C-terminus tethers FtsZ to the membrane. When incorporated inside multi-lamellar tubular liposomes, FtsZ-YFP-mts can assemble Z rings that generate a constriction force. When added to the outside of liposomes, FtsZ-YFP-mts bound and produced concave depressions, bending the membrane in the same direction as the Z ring inside liposomes. Prominent membrane tubules were then extruded at the intersections of concave depressions. We tested the effect of moving the membrane-targeting sequence (mts) from the C-terminus to the N-terminus, which is approximately 180 degrees from the C-terminal tether. When mts-FtsZ-YFP was applied to the outside of liposomes, it generated convex bulges, bending the membrane in the direction opposite to the concave depressions. We conclude that FtsZ protofilaments have a fixed direction of curvature, and the direction of membrane bending depends on which side of the bent protofilament the mts is attached to. This supports models in which the FtsZ constriction force is generated by protofilament bending.
| S-EPMC2782090 | biostudies-literature
Project description:Amphiphilic gold nanoparticles (amph-NPs), composed of gold cores surrounded by an amphiphilic mixed organic ligand shell, are capable of embedding within and traversing lipid membranes. Here we describe a strategy using crosslink-stabilized lipid nanocapsules (NCs) as carriers to transport such membrane-penetrating particles into tumor cells and promote their transfer to intracellular membranes for enhanced radiotherapy of cancer. We synthesized and characterized interbilayer-crosslinked multilamellar lipid vesicles (ICMVs) carrying amph-NPs embedded in the capsule walls, forming Au-NCs. Confocal and electron microscopies revealed that the intracellular distribution of amph-NPs within melanoma and breast tumor cells following uptake of free particles vs Au-NCs was quite distinct and that amph-NPs initially delivered into endosomes by Au-NCs transferred over a period of hours to intracellular membranes through tumor cells, with greater intracellular spread in melanoma cells than breast carcinoma cells. Clonogenic assays revealed that Au-NCs enhanced radiotherapeutic killing of melanoma cells. Thus, multilamellar lipid capsules may serve as an effective carrier to deliver amphiphilic gold nanoparticles to tumors, where the membrane-penetrating properties of these materials can significantly enhance the efficacy of frontline radiotherapy treatments.
| S-EPMC4194056 | biostudies-literature
Project description:Amphiphilic, monolayer-protected gold nanoparticles (NPs) have been shown to enter cells via a non-endocytic, non-disruptive pathway that could be valuable for biomedical applications. The same NPs were also found to insert into a series of model cell membranes as a precursor to cellular uptake, but the insertion mechanism remains unclear. Previous simulations have demonstrated that an amphiphilic NP can insert into a single leaflet of a planar lipid bilayer, but in this configuration all charged end groups are localized to one side of the bilayer and it is unknown if further insertion is thermodynamically favorable. Here, we use atomistic molecular dynamics simulations to show that an amphiphilic NP can reach the bilayer midplane non-disruptively if charged ligands iteratively "flip" across the bilayer. Ligand flipping is a favorable process that relaxes bilayer curvature, decreases the nonpolar solvent-accessible surface area of the NP monolayer, and increases attractive ligand-lipid electrostatic interactions. Analysis of end group hydration further indicates that iterative ligand flipping can occur on experimentally relevant timescales. Supported by these results, we present a complete energy landscape for the non-disruptive insertion of amphiphilic NPs into lipid bilayers. These findings will help guide the design of NPs to enhance bilayer insertion and non-endocytic cellular uptake, and also provide physical insight into a possible pathway for the translocation of charged biomacromolecules.
| S-EPMC6326551 | biostudies-literature
Project description:Laurdan fluorescence, novel spectral fitting, and dynamic light scattering were combined to determine lateral lipid organization in mixed lipid membranes of the oxidized lipid, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC), and each of the three bilayer lipids, 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC), and 1-palmitoyl-2-oleoylphosphatidylcholine (POPC). Second harmonic spectra were computed to determine the number of elementary emissions present. All mixtures indicated two emissions. Accordingly, spectra were fit to two log-normal distributions. Changes with PGPC mole fraction, XPGPC, of the area of the shorter wavelength line and of dynamic light scattering-derived aggregate sizes show that: DPPC and PGPC form component-separated mixed vesicles for XPGPC ≤ 0.2 and coexisting vesicles and micelles for XPGPC > 0.2 in gel and liquid-ordered phases and for all XPGPC in the liquid-disordered phase; POPC and PGPC form randomly mixed vesicles for XPGPC ≤ 0.2 and component-separated mixed vesicles for XPGPC > 0.2. DOPC and PGPC separate into vesicles and micelles. Component segregation is due to unstable inhomogeneous membrane curvature stemming from lipid-specific intrinsic curvature differences between mixing molecules. PGPC is inverse cone-shaped because its truncated tail with a terminal polar group points into the interface. It is similar to and mixes with POPC, also an inverse cone because of mobility of its unsaturated tail. PGPC is least similar to DOPC because mobilities of both unsaturated tails confer a cone shape to DOPC, and PGPC separates form DOPC. DPPC and PGPC do not mix in the liquid-disordered phase because mobility of both tails in this phase renders DPPC a cone. DPPC is a cylinder in the gel phase and of moderate similarity to PGPC and mixes moderately with PGPC.
| S-EPMC7175694 | biostudies-literature
Project description:Phase segregation of membranal components, such as proteins, lipids, and cholesterols, leads to the formation of aggregates or domains that are rich in specific constituents. This process is important in the interaction of the cell with its surroundings and in determining the cell's behavior and fate. Motivated by published experiments on curvature-modulated phase separation in lipid membranes, we formulate a mathematical model aiming at studying the spatial ordering of composition in a two-component biomembrane that is subjected to a prescribed (imposed) geometry. Based on this model, we identified key nondimensional quantities that govern the biomembrane response and performed numerical simulations to quantitatively explore their influence. We reproduce published experimental observations and extend them to surfaces with geometric features (imposed geometry) and lipid phases beyond those used in the experiments. In addition, we demonstrate the possibility for curvature-modulated phase separation above the critical temperature and propose a systematic procedure to determine which mechanism, the difference in bending stiffness or difference in spontaneous curvatures of the two phases, dominates the coupling between shape and composition.
| S-EPMC5394915 | biostudies-literature
Project description:The development of a strategy to investigate interfacial phenomena at lipid membranes is practically useful because most essential biomolecular interactions occur at cell membranes. In this study, a colorimetric method based on cysteine-encapsulated liposomes was examined using gold nanoparticles as a probe to provide a platform to report an enzymatic activity at lipid membranes. The cysteine-encapsulated liposomes were prepared with varying ratios of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and cholesterol through the hydration of lipid films and extrusions in the presence of cysteine. The size, composition, and stability of resulting liposomes were analyzed by scanning electron microscopy (SEM), dynamic light scattering (DLS), nuclear magnetic resonance (NMR) spectroscopy, and UV-vis spectrophotometry. The results showed that the increased cholesterol content improved the stability of liposomes, and the liposomes were formulated with 60 mol % cholesterol for the subsequent experiments. Triton X-100 was tested to disrupt the lipid membranes to release the encapsulated cysteine from the liposomes. Cysteine can induce the aggregation of gold nanoparticles accompanying a color change, and the colorimetric response of gold nanoparticles to the released cysteine was investigated in various media. Except in buffer solutions at around pH 5, the cysteine-encapsulated liposomes showed the color change of gold nanoparticles only after being incubated with Triton X-100. Finally, the cysteine-encapsulated liposomal platform was tested to report the enzymatic activity of phospholipase A2 that hydrolyzes phospholipids in the membrane. The hydrolysis of phospholipids triggered the release of cysteine from the liposomes, and the released cysteine was successfully detected by monitoring the distinct red-to-blue color change of gold nanoparticles. The presence of phospholipase A2 was also confirmed by the appearance of a peak around 690 nm in the UV-vis spectra, which is caused by the cysteine-induced aggregation of gold nanoparticles. The results demonstrated that the cysteine-encapsulated liposome has the potential to be used to investigate biological interactions occurring at lipid membranes.
| S-EPMC9500635 | biostudies-literature
Project description:The Gaussian curvature modulus κ¯ of lipid bilayers likely contributes more than 100 kcal/mol to every cellular fission or fusion event. This huge impact on membrane remodeling energetics might be a factor that codetermines the complex lipid composition of biomembranes through tuning of κ¯. Yet, its value has been measured only for a handful of simple lipids, and no simulation has so far determined it better than a factor of two, rendering a systematic investigation of such enticing speculations impossible. Here we propose a highly accurate method to determine κ¯ in computer simulations. It relies on the interplay between curvature stress and edge tension of partially curved axisymmetric membrane disks and requires determining their closing probability. For a simplified lipid model we obtain κ¯ and its relation to the normal bending modulus κ for membranes differing both in stiffness and spontaneous lipid curvature. The elastic ratio κ¯/κ can be determined with a few percent statistical accuracy. Its value agrees with the scarce experimental data, and its change with spontaneous lipid curvature is compatible with theoretical expectations, thereby granting additional information on monolayer properties. We also show that an alternative determination of these elastic parameters based on moments of the lateral stress profile gives markedly different and unphysical values.
| S-EPMC3309410 | biostudies-literature