Health concerns associated with the advent of nanotechnologies have risen sharply when it was found that particles of nanoscopic dimensions reach the cell lumina. Plasma and organelle lipid membranes, which are exposed to both the incoming and the engulfed nanoparticles, are the primary targets of possible disruptions. However, reported adhesion, invagination and embedment of nanoparticles (NPs) do not compromise the membrane integrity, precluding direct bilayer damage as a mechanism for toxicity. Here it is shown that a lipid membrane can be torn by small enough nanoparticles, thus unveiling mechanisms for how lipid membrane can be compromised by tearing from nanoparticles. Surprisingly, visualization by cryo transmission electron microscopy (cryo-TEM) of liposomes exposed to nanoparticles revealed also that liposomal laceration is prevented by particle abundance. Membrane destruction results thus from a subtle particle-membrane interplay that is here elucidated. This brings into a firmer molecular basis the theorized mechanisms of nanoparticle effects on lipid bilayers and paves the way for a better assessment of nanoparticle toxicity.
We use a coarse-grained molecular dynamics simulation to investigate the interaction between neutral or charged nanoparticles (NPs) and a vesicle consisting of neutral and negatively charged lipids. We focus on the interaction strengths of hydrophilic and hydrophobic attraction and electrostatic interactions between a lipid molecule and an NP. A neutral NP passes through the lipid membrane when the hydrophobic interaction is sufficiently strong. As the valence of the positively charged NP increases, the membrane permeation speed of the NP is increased compared with the neutral NP and charged l…
Lipid nanoemulsions and nanosuspensions are used as flavor carriers and bubble stabilizers in soft drinks and foods, as well as delivery vehicles for lipophilic drugs in pharmaceutics. Common techniques for their formation are the high-pressure and ultrasonic homogenizers. These techniques dissipate most of the input energy, which results in excessive heating and generation of free radicals that might modify sensitive ingredients. Low energy methods are also used in some applications, but they have specific limitations restricting their universal use. In the current study, we propose an altern…
The impact of nanomaterials on lung fluids or on the plasma membrane of living cells has prompted researchers to examine the interactions between nanoparticles and lipid vesicles. Recent studies have shown that nanoparticle-lipid interaction leads to a broad range of structures including supported lipid bilayers (SLB), particles adsorbed at the surface or internalized inside vesicles, and mixed aggregates. Today, there is a need to have simple protocols that can readily assess the nature of structures obtained from particles and vesicles. Here we apply the method of continuous variation for me…
Lipid-based drug delivery systems are considered as promising vehicles for hydrophobic drug compounds. Lipid distribution within the droplet can affect drug loading capacity in these carriers. It is extremely challenging to determine the nanostructure within these carriers through the implementation of the direct experimental methods due to the ultrafine size. Therefore, coarse grained molecular dynamics (MD) simulation was utilized to model different lipid-based nanoparticles of the diameter about 12 nm including solid lipid nanoparticles (SLN), nanoemulsion (NE), and nanostructured lipid car…
We describe several unexpected phenomena, caused by a solid-solid phase transition (gel-to-crystal) typical for all main classes of lipid substances - phospholipids, triglycerides, diglycerides, alkanes, etc. We discovered that this transition leads to spontaneous formation of a network of nanopores, spreading across the entire lipid structure. These nanopores are spontaneously impregnated (flooded) by water when appropriate surfactants are present, thus fracturing the lipid structure at a nano-scale. As a result, spontaneous disintegration of the lipid into nanoparticles or formation of doubl…
Cells offer numerous inspiring examples where proteins and membranes combine to form complex structures that are key to intracellular compartmentalization, cargo transport, and specialization of cell morphology. Despite this wealth of examples, we still lack the design principles to control membrane morphology in synthetic systems. Here we show that even the relatively simple case of spherical nanoparticles binding to lipid-bilayer membrane vesicles results in a remarkably rich set of morphologies that can be controlled quantitatively via the particle binding energy. We find that when the bind…
Bio-conjugated nanomaterials play a promising role in the development of novel supramolecular structures, molecular machines, and biosensing devices. In this study, lipid-conjugated gold nanoparticles were synthesized and allowed to form a self-assembled monolayer structure. The nanoparticles were prepared by a phase transfer method, which involved the reduction of potassium tetrachloroaurate (III) by sodium citrate in an aqueous solution and the simultaneous transfer of the reduced species to an organic medium containing DMPC (1,2-dimyristoyl-sn-glycero-3-phosphocholine). The gold nanoparticl…
Effective and controlled drug delivery systems with on-demand release abilities and biocompatible properties receive enormous attention for biomedical applications. Here, we describe a novel inorganic-organic hybrid material with a strikingly high organic content of almost 50 wt%. The colloidal periodic mesoporous organosilica (PMO) nanoparticles synthesized in this work consist entirely of curcumin and ethane derivatives serving as constituents that are crosslinked by siloxane bridges, without any added silica. These mesoporous curcumin nanoparticles (MCNs) exhibit very high surface areas (ov…
The computational study of the interaction between charged, ligand-protected metal nanoparticles and model lipid membranes has been recently addressed both at atomistic and coarse grained level. Here we compare the performance of three versions of the coarse grained Martini force field at describing the nanoparticle-membrane interaction. The three coarse-grained models differ in terms of treatment of long-range electrostatic interactions and water polarizability. The NP-membrane interaction consists in the transition from a metastable NP- membrane complex, in which the NP is only partially emb…
Letter to the Editor Concerning "Simultaneous, Single-Particle Measurements of Size and Loading Give Insights into the Structure of Drug-Delivery Nanoparticles"
Preparation of nanoemulsions of triglyceride oils in water usually requires high mechanical energy and sophisticated equipment. Recently, we showed that alpha-to-beta (viz. gel-to-crystal) phase transition, observed with most lipid substances (triglycerides, diglycerides, phospholipids, alkanes, etc.), may cause spontaneous disintegration of micro-particles of these lipids, dispersed in aqueous solutions of appropriate surfactants, into nanometer particles/drops using a simple cooling/heating cycle of the lipid dispersion (Cholakova et al. ACS Nano 14 (2020) 8594). In the current study we show…
In recent experiments [T. Basta et al., Proc. Natl. Acad. Sci. U.S.A. 111, 670 (2014)] lipids and membrane proteins were observed to self-assemble into membrane protein polyhedral nanoparticles (MPPNs) with a well-defined polyhedral protein arrangement and characteristic size. We develop a model of MPPN self-assembly in which the preferred symmetry and size of MPPNs emerge from the interplay of protein-induced lipid bilayer deformations, topological defects in protein packing, and thermal effects. With all model parameters determined directly from experiments, our model correctly predicts the …
Nanoparticles with hydrophobic capping ligands and amphiphilic phospholipids are both found to self-assemble into monolayer films when deposited on the air water interface. By separately measuring the anisotropic stress response of these films under uniaxial compression, we obtain both the 2D compressive and shear moduli of a range of different thin nanoparticle and phospholipid films. The compressive moduli of both nanoparticle and lipid films in the solid phase are on the same order of magnitude, whereas the shear moduli of the lipid films are found to be significantly lower. Additionally th…
Using computer simulations we show that lipid membranes can mediate linear aggregation of spherical nanoparticles binding to it for a wide range of biologically relevant bending rigidities. This result is in net contrast with the isotropic aggregation of nanoparticles on fluid interfaces or the expected clustering of isotropic insertions in biological membranes. We present a phase diagram indicating where linear aggregation is expected, and compute explicitly the free energy barriers associated with linear and isotropic aggregation. Finally, we provide simple scaling arguments to explain this …
Inhaled nanoparticles traveling through the airways are able to reach the respiratory zone of the lungs. In such event, the incoming particles first enter in contact with the liquid lining the alveolar epithelium, the pulmonary surfactant. The pulmonary surfactant is composed of lipids and proteins that are assembled into large vesicular structures. The question of the nature of the biophysicochemical interaction with the pulmonary surfactant is central to understand how the nanoparticles can cross the air-blood barrier. Here we explore the phase behavior of sub-100 nm particles and surfactant…
In this work we describe a set of Coarse-grained (CG) tools that allow to simulate the uptake of the nanoparticles (NPs) coated with proteins by a lipid bilayer. We describe a CG model to calculate the adsorption energies and the most favorable adsorption orientations of proteins onto a hydrophobic NP. The proposed method is then used to calculate the adsorption energies of two common proteins in human blood onto neutral and negative charged NPs. We also report the effect of the NP radius on the adsorption energies and validate the proposed methodology against full atomistic simulations. We al…
Supported lipid bilayers have been studied intensively over the past two decades. In this work, we study the diffusion of single gold nanoparticles (GNPs) with diameter of 20 nm attached to GM1 ganglioside or DOPE lipids at different concentrations in supported DOPC bilayers. The indefinite photostability of GNPs combined with the high sensitivity of interferometric scattering microscopy (iSCAT) allows us to achieve 1.9 nm spatial precision at 1 ms temporal resolution, while maintaining long recording times. Our trajectories visualize strong transient confinements within domains as small as 20…
Inhaled nanoparticles (< 100 nm) reaching the deep lung region first interact with the pulmonary surfactant, a thin lipid film lining the alveolar epithelium. To date, most biophysical studies have focused on particle induced modifications of the film interfacial properties. In comparison, there is less work on the surfactant bulk properties, and on their changes upon particle exposure. Here we study the viscoelastic properties of a biomimetic pulmonary surfactant in the presence of various engineered nanoparticles. The microrheology technique used is based on the remote actuation of micron-si…
Although promising for biomedicine, the clinical translation of inorganic nanoparticles (NPs) is limited by low biocompatibility and stability in biological fluids. A common strategy to circumvent this drawback consists in disguising the active inorganic core with a lipid bilayer coating, reminiscent of the structure of the cell membrane to redefine the chemical and biological identity of NPs. While recent reports introduced membrane coating procedures for NPs, a robust and accessible method to quantify the integrity of the bilayer coverage is not yet available. To fill this gap, we prepared S…
Studies have shown that following exposure to particulate matter, the ultrafine fraction (< 100 nm) may deposit along the respiratory tract down to the alveolar region. To assess the effects of nanoparticles in the lungs, it is essential to address the question of their biophysicochemical interaction with the different pulmonary environments, including the lung lining fluids and the epithelia. Here we examine one of these interactive scenarios and study the role of supported lipid bilayers (SLB) on the fate of 40 nm fluorescent silica particles towards living cells. We first study the particle…
Amphiphilic molecules such as surfactants, lipids and block copolymers can be assembled into bilayers and form vesicles. Fluorescent membrane labeling methods require the use of dye molecules that can be inserted in the bilayers at different stages of the synthesis. To our knowledge there is no generalized method for labeling preformed vesicles. Herein we develop a versatile protocol that is suitable to both surfactant and lipid preformed vesicles and requires no separation or purification steps. Based on the lipophilic carbocyanine green dye PKH67, the methodology is assessed on zwitterionic …
Membrane organization is essential for cellular functions such as signal transduction and membrane trafficking. A major challenge is to understand the lateral heterogeneous structures in membranes and membrane fluidity in the presence of inclusions. Based on a considerable amount of experimental evidence for lateral organization of lipid membranes which share astonishingly similar features in the presence of different inclusions, we first present a general model system of bilayer membranes embedded by nanosized inclusions, and explain experimental findings. Here, the hydrophobic inclusions are…
Internalization of particles by cells plays a crucial role for adsorbing nutrients and fighting infection. Endocytosis is one of the most important mechanisms of the particles uptake which encompass multiple pathways. Although endocytosis is a complex mechanism involving biochemical signaling and active force generation, the energetic cost associated to the large deformations of the cell membrane wrapping around the foreign particle is an important factor controlling this process, which can be studied using quantitative physical models. Of particular interest is the competition between membran…
