Self-assembly Of Lipid Molecules Research Articles

Self-Assembly of Lipid Molecules under Shear Flows: A Dissipative Particle Dynamics Simulation Study.

The self-assembly of lipid molecules in aqueous solution under shear flows was investigated using the dissipative particle dynamics simulation method. Three cases were considered: zero shear flow, weak shear flow and strong shear flow. Various self-assembled structures, such as double layers, perforated double layers, hierarchical discs, micelles, and vesicles, were observed. The self-assembly behavior was investigated in equilibrium by constructing phase diagrams based on chain lengths. Results showed the remarkable influence of chain length, shear flow and solution concentration on the self-assembly process. Furthermore, the self-assembly behavior of lipid molecules was analyzed using the system energy, particle number and shape factor during the dynamic processes, where the self-assembly pathways were observed and analyzed for the typical structures. The results enhance our understanding of biomacromolecule self-assembly in a solution and hold the potential for applications in biomedicine.

A short review on the applicability and use of cubosomes as nanocarriers.

Cubosomes are nanostructured lipid-based particles that have gained significant attention in the field of drug delivery and nanomedicine. These unique structures consist of a three-dimensional cubic lattice formed by the self-assembly of lipid molecules. The lipids used to construct cubosomes are typically nonionic surfactants, such as monoolein, which possess both hydrophilic and hydrophobic regions, allowing them to form stable, water-dispersible nanoparticles. One of the key advantages of cubosomes is their ability to encapsulate and deliver hydrophobic as well as hydrophilic drugs. The hydrophobic regions of the lipid bilayers provide an ideal environment for incorporating lipophilic drugs, while the hydrophilic regions can encapsulate water-soluble drugs. This versatility makes cubosomes suitable for delivering a wide range of therapeutic agents, including small molecules, proteins, peptides, and nucleic acids. The unique structure of cubosomes also offers stability and controlled release benefits. The lipid bilayers provide a protective barrier, shielding the encapsulated drugs from degradation and improving their stability. Moreover, the cubic lattice arrangement enables the modulation of drug release kinetics by varying the lipid composition and surface modifications. This allows for the development of sustained or triggered drug release systems, enhancing therapeutic efficacy and reducing side effects. Furthermore, cubosomes can be easily modified with targeting ligands or surface modifications to achieve site-specific drug delivery, enhancing therapeutic selectivity and reducing off-target effects. In conclusion, cubosomes offer a versatile and promising platform for the delivery of therapeutic agents. In this manuscript, we will highlight some of these applications.

Rapid Production and Purification of Dye-Loaded Liposomes by Electrodialysis-Driven Depletion.

Liposomes are spherical-shaped vesicles that enclose an aqueous milieu surrounded by bilayer or multilayer membranes formed by self-assembly of lipid molecules. They are intensively exploited as either model membranes for fundamental studies or as vehicles for delivery of active substances in vivo and in vitro. Irrespective of the method adopted for production of loaded liposomes, obtaining the final purified product is often achieved by employing multiple, time consuming steps. To alleviate this problem, we propose a simplified approach for concomitant production and purification of loaded liposomes by exploiting the Electrodialysis-Driven Depletion of charged molecules from solutions. Our investigations show that electrically-driven migration of charged detergent and dye molecules from solutions that include natural or synthetic lipid mixtures leads to rapid self-assembly of loaded, purified liposomes, as inferred from microscopy and fluorescence spectroscopy assessments. In addition, the same procedure was successfully applied for incorporating PEGylated lipids into the membranes for the purpose of enabling long-circulation times needed for potential in vivo applications. Dynamic Light Scattering analyses and comparison of electrically-formed liposomes with liposomes produced by sonication or extrusion suggest potential use for numerous in vitro and in vivo applications.

Particle-based simulations of bilayer membranes: self-assembly, structural analysis, and shock-wave damage

We report on the results of particle-based, coarse-grained molecular dynamics simulations of amphiphilic lipid molecules in aqueous environment where the membrane structures at equilibrium are subsequently exposed to strong shock waves, and their damage is analyzed. The lipid molecules self-assemble from unbiased random initial configurations to form stable bilayer membranes, including closed vesicles. During self-assembly of lipid molecules, we observe several stages of clustering, starting with many small clusters of lipids, gradually merging together to finally form one single bilayer membrane. We find that the clustering of lipids sensitively depends on the hydrophobic interaction \(h_\mathrm{c}\) of the lipid tails in our model and on temperature T of the system. The self-assembled bilayer membranes are quantitatively analyzed at equilibrium with respect to their degree of order and their local structure. We also show that—by analyzing the membrane fluctuations and using a linearized theory— we obtain area compression moduli \(K_\mathrm{A}\) and bending stiffnesses \(\kappa _\mathrm{B}\) for our bilayer membranes which are within the experimental range of in vivo and in vitro measurements of biological membranes. We also discuss the density profile and the pair correlation function of our model membranes at equilibrium which has not been done in previous studies of particle-based membrane models. Furthermore, we present a detailed phase diagram of our lipid model that exhibits a sol–gel transition between quasi-solid and fluid domains, and domains where no self-assembly of lipids occurs. In addition, we present in the phase diagram the conditions for temperature T and hydrophobicity \(h_\mathrm{c}\) of the lipid tails of our model to form closed vesicles. The stable bilayer membranes obtained at equilibrium are then subjected to strong shock waves in a shock tube setup, and we investigate the damage in the membranes due to their interaction with shock waves. Here, we find a transition from self-repairing membranes (reducing their damage after impact) and permanent (irreversible) damage, depending on the shock front speed. The here presented idea of using coarse-grained (CG) particle models for soft matter systems in combination with the investigation of shock-wave effects in these systems is a quite new approach.

English

Introduction The fabrication methods and functionalization of lipid tubes are described. The fabrication methods of lipid tubes were classified into three categories, i.e. self-assembly of lipid molecules, microfluidic way to form tubes and stretching of giant v esicles using an electric field. The functionalization of lipid tubes was summarized as metallization and deposition of inor ganic silica onto tube surface, encapsulation of nanoparticles into hollow cylindrical tube of tubular microstructures, and embedding nanoparticles into the wall of lipid tubes to form functional nanocomposites or nanostructures. The applications of these nano- and microstructures are also given. This review gives a brief overview of the interesting field of lipid tubes. Conclusion The fabrication of tubular microstructures demonstrated the precise self-assembly property of lipid molecules. To explore a new universal fabrication method for lipid tubes is still a direction of this field. Templating technology using lipid tubular microstructures is a promising route to make diverse nanostructures. Duo to the high biocompatibility of lipid tubes, they can be designed as drug carriers to encapsulate hydrophilic molecules inside the tube or hydrophobic molecules within the lipid bilay er for drug delivery in biomedical research.

Biomimetic nanoparticles: preparation, characterization and biomedical applications

Mimicking nature is a powerful approach for developing novel lipid-based devices for drug and vaccine delivery. In this review, biomimetic assemblies based on natural or synthetic lipids by themselves or associated to silica, latex or drug particles will be discussed. In water, self-assembly of lipid molecules into supramolecular structures is fairly well understood. However, their self-assembly on a solid surface or at an interface remains poorly understood. In certain cases, hydrophobic drug granules can be dispersed in aqueous solution via lipid adsorption surrounding the drug particles as nanocapsules. In other instances, hydrophobic drug molecules attach as monomers to borders of lipid bilayer fragments providing drug formulations that are effective in vivo at low drug-to-lipid-molar ratio. Cationic biomimetic particles offer suitable interfacial environment for adsorption, presentation and targeting of biomolecules in vivo. Thereby antigens can effectively be presented by tailored biomimetic particles for development of vaccines over a range of defined and controllable particle sizes. Biomolecular recognition between receptor and ligand can be reconstituted by means of receptor immobilization into supported lipidic bilayers allowing isolation and characterization of signal transduction steps.

Molecular Mechanisms of Peptide Translocation Across Micelles: A Case Study of Cell-Penetrating Peptide and Antimicrobial Peptide

We investigated the molecular mechanisms of short peptides across plasma membranes by studying their varying ability in permeating through membrane-mimetic systems. Three short peptides are selected for this study: penetratin is a cell-penetrating peptide and temporin A and KSL are antimicrobials (AMP). Their detailed interactions with SDS and DPC micelles, sometimes associated with their conformational changes, which govern their ability in translocation, are revealed by all-atomistic molecular simulations with explicit solvent models and free energy calculation of peptide insertion. We found that penetratin undergoes conformational changes upon binding and insertion and it causes less structural disturbance in the self-assembly of lipid molecules in micelles, which is in accordance with its macroscopic non-invasive behavior when it passes through membranes of mammalian cells. In contrast, temporin A and KSL peptides tend to destroy the self-assembly of lipid micelles through strong hydrophobic interaction in the former and electrostatic interactions in the latter. Our investigation addresses some of the speculation regarding the molecular mechanisms of the toxicity in short peptides.

Rapid and efficient method for the size separation of homogeneous fluorescein-encapsulating liposomes

Liposomes are colloidal structures formed by the self-assembly of lipid molecules in solution into spherical, self-closed structures through their amphiphilic properties. All liposome preparation protocols reported consist of several steps of preparation, homogenization, and purification, which are labor-intensive, arduous, and lengthy to execute. In this work, a new procedure has been developed to reduce the time of the postrehydration sizing of liposomes from multilamellar vesicles, while improving the uniformity of the resulting liposomes produced and achieving high encapsulation efficiencies. For the homogenization step, the typically used method of filter extrusion was substituted by centrifugation. Purification of liposomes to eliminate nonencapsulated molecules and lipids is routinely carried out via gel permeation chromatography, an extremely lengthy procedure, and in the method we report, this lengthy step was replaced by the use of molecular-weight cut-off filters. Using this novel method, large unilamellar vesicles were produced and the time required, postrehydration, was dramatically reduced from almost 48 to less than 2 hours, with a highly uniformly sized population of liposomes being produced—the homogeneity of the liposome population achieved using our method was 99%, as compared to 88% attained by using the traditional method of production. We have used this approach to encapsulate fluorescein isothiocyanate (FITC), and 160,000 FITC molecules were encapsulated and the liposomes were demonstrated to be stable for at least 10 weeks at 4°C.

Nanoengineering Artificial Lipid Envelopes Around Adenovirus by Self-Assembly

We have developed a novel, reproducible, and facile methodology for the construction of artificial lipid envelopes for adenoviruses (Ad) by self-assembly of lipid molecules around the viral capsid. No alteration of the viral genome or conjugation surface chemistry at the virus capsid was necessary, therefore difficulties in production and purification associated with generating most surface-modified viruses can be eliminated. Different lipid bilayer compositions produced artificially enveloped Ad with physicochemical and biological characteristics determined by the type of lipid used. Physicochemical characteristics such as vector size, degree of aggregation, stability, and surface charge of the artificially enveloped Ad were correlated to their biological (gene transfer) function. In monolayer cell cultures, binding to the coxsackie and adenovirus receptor (CAR) was blocked using a zwitterionic envelope, whereas enhanced binding to the cell membrane was achieved using a cationic envelope. Envelopment of Ad by both zwitterionic and cationic lipid bilayers led to almost complete ablation of gene expression in cell monolayers, due to blockage of virion endosomal escape. Alternatively, artificial Ad envelopes built from lipid bilayers at the fluid phase in physiological conditions led to enhanced penetration of the vectors inside a three-dimensional tumor spheroid cell culture model and delayed gene expression in the tumor spheroid compared to nonenveloped adenovirus. These results indicate that construction of artificial envelopes for nonenveloped viruses by lipid bilayer wrapping of the viral capsids constitutes a general strategy to rationally engineer viruses at the nanoscale with control over their biological properties.

Functional assays of membrane-bound proteins with SAMDI-TOF mass spectrometry.

Functional assays of membrane-bound proteins with SAMDI-TOF mass spectrometry.

Multiscale modeling of lipids and lipid assemblies

Division of Physical Chemistry, Stockholm University, Sweden A multiscale modeling approach is developed for simulations of lipids and lipid assemblies on mesoscale. First, molecular dynamics simulation of initially disordered system of lipid molecules in water within an all-atom force field are carried out. On the next stage, radial distribution functions (RDFs) obtained from the molecular dynamics simulation are used to build a coarse-grained lipid model, with effective interaction potentials computed by the inverse Monte Carlo method. The computed effective potentials reproduce, for the coarse-grained model in an implicit solvent, exactly the same RDFs as those obtained in fully atomistic simulations. Due to greatly reduced number of degrees of freedom, such coarse-grained model can be used to simulate systems consisting of many thousands of lipids. This approach has been applied to build a 10-site DMPC lipid model from the all-atomic model defined by the CHARMM force field. The constructed lipid coarsegrained model reproduces well properties of a plain lipid bilayer. Being simulated without boundary conditions, a bilayer fragment adopts a shape of bicell or vesicle, depending on the number of lipids in the fragment. The process of self-assembly of lipid molecules is also demonstrated, which results in different structures depending on the initial number and concentrations of lipids.

Self-Assembly and Subsequent Accumulation of Lipid Nanotubes at Oil/Water Interfaces

We utilized oil/water interfaces as a new field to produce lipid nanotubes (LNTs), which are formed by the self-assembly of lipid molecules, and possess hollow nanometer-wide cylindrical structures. Compared to the self-assembling field in bulk water, oil/water interfaces produced shorter lipids nanotubes less than 10 microm long more efficiently. In addition, we found that the oil/water interface accumulates lipid nanotubes spontaneously. This methodology is favorable to fabricate LNTs as new nano-fluidic devices, or sensors that require accumulation and alignment in two dimensions.

Substrate-induced structural changes in electrode-adsorbed lipid layers: A self-consistent field theory

In this paper, the adsorption and self-assembly of lipid molecules on solid-water interfaces are modelled to produce thermodynamic explanations for the observed phase transitions. In particular, structural changes are studied in the adsorbed layer when, at a constant amount of lipids at the surface, the surface properties are altered. A Self-Consistent Field approach is used in which interfacial equilibrium conformations of model-lipid molecules are found with Flory-Huggins-type approximations. This treatment involves Markov-type chain statistics (Rotational Isomeric State scheme) combined with a local Mean Field approximation. Such a theory is applicable well above the gel-to-liquid phase transition temperature. Taking the mercury-water interface as an example, decreasing or increasing the applied potential with respect to the pzc renders the surface less hydrophobic. This changes the interaction energies between the surface and the various components of the lipid and solution. As a result a complicated reorientation process takes place for constant lipids on the surface which depends, among other things, on the type of lipid used. For head groups with a rather high surface affinity, two transitions are predicted. The first one originates from a displacement of tail segments by head group segments at a potential where the tail segments still have a high surface affinity compared to the water leaving an inhomogeneous adsorbed layer. At the second transition the surface affinity of the tails is overtaken by that of the water molecules which leads to a partially almost bare (i.e. water covered) surface in equilibrium with adsorbed bilayer structures. For head groups with a low surface affinity at the pzc, the first and second phase transitions coincide.

Difference in packing properties between iso and anteiso methyl-branched fatty acids as revealed by incorporation into the membrane lipids of Acholeplasma laidlawii strain A

Acholeplasma laidlawii strain A was grown on the long-chain, branched, saturated fatty acids 12-methyltetradecanoic acid (anteiso-C 15), 14-methylhexadecanoic acid (anteiso-C 17), 13-methyltetradecanoic acid (iso-C 15) and 15-methylhexadecanoic acid (iso-C 17), and on the branched-chain fatty acid precursors 2-methylbutanoic acid (anteiso-C 5) and 3-methylbutanoic acid (iso-C 5). The membrane lipid composition as a function of the fatty acid supplement and the growth temperature was determined: (1) The ratio between the two dominating lipids, monoglucosyldiacylglycerol and diglucosyldiacylglycerol, is decreased when anteiso acyl chains replace iso acyl chains in the lipids, and when the acyl chains are elongated from 15 to 17 carbon atoms; (2) the ratio iso / anteiso acyl chains is reduced when the growth temperature is decreased; (3) the average length of the de novo synthesized branched fatty acids is decreased when the growth temperature is lowered, and when anteiso-C 5 is exchanged for iso-C 5 in the growth medium. The lipid regulation mechanisms are interpreted in terms of lipid molecular geometry and self-assembly of lipid molecules. It is concluded that iso and anteiso fatty acids have distinctively different packing properties in a biological membrane, and they mimic straight-chain saturated and cis-monounsaturated fatty acids, respectively, as seen by the way they affect the physicochemical properties of membrane lipids and by the way they are used in lipid regulation mechanisms.