To understand how lipid architecture determines the lipid bilayer structure and its mechanics, we implement a molecularly detailed model that uses the self-consistent field theory. This numerical model accurately predicts parameters such as Helfrichs mean and Gaussian bending modulus kc and k̄ and the preferred monolayer curvature J(0)(m), and also delivers structural membrane properties like the core thickness, and head group position and orientation. We studied how these mechanical parameters vary with system variations, such as lipid tail length, membrane composition, and those parameters that control the lipid tail and head group solvent quality. For the membrane composition, negatively charged phosphatidylglycerol (PG) or zwitterionic, phosphatidylcholine (PC), and -ethanolamine (PE) lipids were used. In line with experimental findings, we find that the values of kc and the area compression modulus kA are always positive. They respond similarly to parameters that affect the core thickness, but differently to parameters that affect the head group properties. We found that the trends for k̄ and J(0)(m) can be rationalised by the concept of Israelachivili's surfactant packing parameter, and that both k̄ and J(0)(m) change sign with relevant parameter changes. Although typically k̄ < 0, membranes can form stable cubic phases when the Gaussian bending modulus becomes positive, which occurs with membranes composed of PC lipids with long tails. Similarly, negative monolayer curvatures appear when a small head group such as PE is combined with long lipid tails, which hints towards the stability of inverse hexagonal phases at the cost of the bilayer topology. To prevent the destabilisation of bilayers, PG lipids can be mixed into these PC or PE lipid membranes. Progressive loading of bilayers with PG lipids lead to highly charged membranes, resulting in J(0)(m) >> 0, especially at low ionic strengths. We anticipate that these changes lead to unstable membranes as these become vulnerable to pore formation or disintegration into lipid disks.

A fluorescence leakage assay was used in a high-throughput setup to obtain information on the phospholipid vesicle leakage induced by the addition of silica nanoparticles. We showed that this method can be used not only to scan for the conditions under which leakage occurs, but also to obtain quantitative information on the interaction between these nanoparticles and the phospholipid membranes.The society is increasingly worried about the impact of engineered nanoparticles (NPs) on the environment and human health. An increasing number of products contain these particles, but knowledge about the risks of NPs is still limited. Multiple studies have focused on the effect of the exposure of various NP species in a variety of systems such as aquatic 13 or soil systems, 4,5 or systems where animals are exposed directly to air-borne particles. 6,7 However, owing to their size, NPs dissolve more quickly in water than do their larger counterparts. As a result, the concentration of dissolved molecules or ions close to the surface is higher compared to the bulk concentration. In particular, when highly dissolvable particles such as silver or zinc oxide are investigated, it is difficult to distinguish between the effect of the particles themselves and the relatively high ion concentration close to the particle surface.Many studies have shown the toxic effects of particles on various organisms. 8 However, prediction of the toxic effects of exposure to an unknown particle remains impossible, even if its physicochemical characteristics such as size, specific surface area, or surface charge and chemistry are known. The possible mechanisms that are determined by these physicochemical properties involve nonspecific interactions. To clarify these mechanisms, we began to investigate the interaction between NPs and the phospholipid membrane. If we can predict if, how, and under what conditions a particle affects a cell membrane, we will know what effects of NPs need to be determined to predict their toxicity. In this research, we wish to clarify the mechanisms involved in the interaction between SiO 2 NPs and a phospholipid membrane and find out how these are influenced by the physicochemical conditions and properties of the particles. Results from our self-consistent field (SCF) modeling (unpublished results) show that the effect of a negative particle charge on the interaction with lipid membranes is twofold: a more highly charged particle attracts the zwitterionic phosphocholine (PC) headgroups more strongly, but is also repelled more strongly owing to the stronger confinement of the electrical double layer that surrounds the particle. Variation of the pH allows us to change the charge on the particles and to study these effects of attraction and repulsion. In our study, we used silica particles of various sizes in combination with 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and mixed DOPC/1,2-dioleoyl-sn-glycero-3-phospho-(1¤-rac-glycerol) (DOPG) phospholipid membranes. Silica particles were chosen because of their low solu...

We studied the interactions of silica and titanium dioxide nanoparticles with phospholipid membranes and show how electrostatics plays an important role. For this, we systematically varied the charge density of both the membranes by changing their lipid composition and the oxide particles by changing the pH. For the silica nanoparticles, results from our recently presented fluorescence vesicle leakage assay are combined with data on particle adsorption onto supported lipid bilayers obtained by optical reflectometry. Because of the strong tendency of the TiO2 nanoparticles to aggregate, the interaction of these particles with the bilayer was studied only in the leakage assay. Self-consistent field (SCF) modeling was applied to interpret the results on a molecular level. At low charge densities of either the silica nanoparticles or the lipid bilayers, no electrostatic barrier to adsorption exists. However, the adsorption rate and adsorbed amounts drop with increasing (negative) charge densities on particles and membranes because of electric double-layer repulsion, which is confirmed by the effect of the ionic strength. SCF calculations show that charged particles change the structure of lipid bilayers by a reorientation of a fraction of the zwitterionic phosphatidylcholine (PC) headgroups. This explains the affinity of the silica particles for pure PC lipid layers, even at relatively high particle charge densities. Particle adsorption does not always lead to the disruption of the membrane integrity, as is clear from a comparison of the leakage and adsorption data for the silica particles. The attraction should be strong enough, and in line with this, we found that for positively charged TiO2 particles vesicle disruption increases with increasing negative charge density on the membranes. Our results may be extrapolated to a broader range of oxide nanoparticles and ultimately may be used for establishing more accurate nanoparticle toxicity assessments and drug-delivery systems.

To perform its barrier function, the lipid bilayer membrane requires a robust resistance against pore formation. Using a self-consistent field (SCF) theory and a molecularly detailed model for membranes composed of charged or zwitterionic lipids, it is possible to predict structural, mechanical, and thermodynamical parameters for relevant lipid bilayer membranes. We argue that the edge energy in membranes is a function of the spontaneous lipid monolayer curvature, the mean bending modulus, and the membrane thickness. An analytical Helfrich-like model suggests that most bilayers should have a positive edge energy. This means that there is a natural resistance against pore formation. Edge energies evaluated explicitly in a two-gradient SCF model are consistent with this. Remarkably, the edge energy can become negative for phosphatidylglycerol (e.g., dioleoylphosphoglycerol) bilayers at a sufficiently low ionic strength. Such bilayers become unstable against the formation of pores or the formation of lipid disks. In the weakly curved limit, we study the curvature dependence of the edge energy and evaluate the preferred edge curvature and the edge bending modulus. The latter is always positive, and the former increases with increasing ionic strength. These results point to a small window of ionic strengths for which stable pores can form as too low ionic strengths give rise to lipid disks. Higher order curvature terms are necessary to accurately predict relevant pore sizes in bilayers. The electric double layer overlap across a small pore widens the window of ionic strengths for which pores are stable.