Per Lyngs Hansen

Interactions between a Polystyrene Particle and Hydrophilic and Hydrophobic Surfaces in Aqueous Solutions

The interaction between a colloidal polystyrene particle mounted on an AFM cantilever and a hydrophilic and a hydrophobic surface in aqueous solution is investigated. Despite the apparent simplicity of these two types of systems a variety of different types of interactions are observed. The system containing the polystyrene particle and a hydrophilic surface shows DLVO-like interactions characteristic of forces between charged surfaces. However, when the surface is hydrophobized the interaction changes dramatically and shows evidence of a bridging air bubble being formed between the particle and the surface. For both sets of systems, plateaus of constant force in the force curves are obtained when the particle is retracted from the surface after being in contact. These events are interpreted as a number of individual polystyrene molecules that are bridging the polystyrene particle and the surface. The plateaus of constant force are expected for pulling a hydrophobic polymer in a bad (hydrophilic) solvent. The plateau heights are found to be of uniform spacing and independent of the type of surface, which suggests a model by which collapsed polymers are extended into the aqueous medium. This model is supported by a full stretching curve showing also the backbone elasticity and a stretching curve obtained in pentanol, where the plateau changes to a nonlinear force response, which is typical for a polymer in a good or neutral solvent. We suggest that these polymer bridges are important in particular for the interaction between polystyrene and the hydrophilic surface, where they to some extent counteract the long-range electrostatic repulsion.

Activation of interfacial enzymes at membrane surfaces

A host of water-soluble enzymes are active at membrane surfaces and in association with membranes. Some of these enzymes are involved in signalling and in modification and remodelling of the membranes. A special class of enzymes, the phospholipases, and in particular secretory phospholipase A(2) (sPLA(2)), are only activated at the interface between water and membrane surfaces, where they lead to a break-down of the lipid molecules into lysolipids and free fatty acids. The activation is critically dependent on the physical properties of the lipid-membrane substrate. A topical review is given of our current understanding of the physical mechanisms responsible for activation of sPLA(2) as derived from a range of different experimental and theoretical investigations.

Force trace hysteresis and temperature dependence of bridging nanobubble induced forces between hydrophobic surfaces

An atomic force microscope and the colloidal probe technique are used to probe the interaction between a hydrophobic particle and a hydrophobic surface in water. The characteristics of the observed force curves strongly suggest that a gas bubble is formed when the particle is moved toward the surface and that the bubble ruptures when the particle subsequently is retracted from the surface. We demonstrate that this type of interaction is not unique for hydrophobic surfaces in water since the interaction between hydrophilic surfaces in air provides very similar force curves. However, the interaction between hydrophobic surfaces vanish if water is replaced by an organic solvent with low polarity. The bridging bubble model is employed to explain the hysteresis observed between approach and retraction force traces and experimental conditions where the hysteresis can be almost eliminated are identified. Finally, it is demonstrated that the hydrophobic interaction is strongly temperature dependent and this dependence can be attributed mainly to the decreasing solubility of air in water with increasing temperature.

Applying a potential across a biomembrane: electrostatic contribution to the bending rigidity and membrane instability.

We investigate the effect on biomembrane mechanical properties due to the presence an external potential for a nonconductive incompressible membrane surrounded by different electrolytes. By solving the Debye-Hückel and Laplace equations for the electrostatic potential and using the relevant stress-tensor we find (1) in the small screening length limit, where the Debye screening length is smaller than the distance between the electrodes, the screening certifies that all electrostatic interactions are short range and the major effect of the applied potential is to decrease the membrane tension and increase the bending rigidity; explicit expressions for electrostatic contribution to the tension and bending rigidity are derived as a function of the applied potential, the Debye screening lengths, and the dielectric constants of the membrane and the solvents. For sufficiently large voltages the negative contribution to the tension is expected to cause a membrane stretching instability. (2) For the dielectric limit, i.e., no salt (and small wave vectors compared to the distance between the electrodes), when the dielectric constant on the two sides are different the applied potential induces an effective (unscreened) membrane charge density, whose long-range interaction is expected to lead to a membrane undulation instability.

Characterization of fluorinated catansomes: a promising vector in drug-delivery.

Catansomes, which are vesicles prepared from mixtures of oppositely charged surfactants, have been suggested as effective alternatives to phospholipid vesicles, i.e., liposomes, in applications such as drug-delivery. This is mainly due to their enhanced chemical and physical stability as well as to their relatively easy preparation, which is an advantage for large-scale productions. In this study we have investigated catansomes prepared from a perfluorinated anionic surfactant (sodium perfluorooctanoate) premixed with a hydrogenated cationic surfactant (dodecyltrimethylammonium bromide or 1-dodecylpyridinium chloride). The aim was to gain insights into the physicochemical properties of these systems, such as size, stability, surface charge, and membrane morphology, which are essential for their use in drug-delivery applications. The catansomes were mostly unilamellar and 100-200 nm in size, and were stable for more than five months at room temperature. After loading the catansomes with the fluorescent marker calcein, they were found to exhibit an appreciable encapsulation efficiency and a low calcein leakage over time. The addition of fatty acids to calcein-loaded catansomes considerably promoted the release of calcein, and the rate and efficiency of calcein release were found to be proportional to the fatty acid concentration and chain length. Our results prove the feasibility of utilizing catansomes as drug-delivery vehicles as well as provide a means to efficiently release the encapsulated load.

Propofol modulates the lipid phase transition and localizes near the headgroup of membranes.

The compound 2,6-diisopropylphenol (Propofol, PRF) is widely used for inducing general anesthesia, but the mechanism of PRF action remains relatively poorly understood at the molecular level. This work examines the possibility that a potential mode of action of PRF is to modulate the lipid order in target membranes. The effect on monolayers and bilayers of dipalmitoyl-sn-glycero-3-phosphorylcholine (DPPC) was probed using Langmuir monolayer isotherms, differential scanning calorimetry (DSC), isothermal titration calorimetry (ITC) and molecular dynamics (MD) simulations. Increasing amounts of PRF in a DPPC monolayer causes a decrease in isothermal compressibility modulus at the phase transition. A partition constant for PRF in DPPC liposomes on the order of K≈1500 M(-1) was found, and the partitioning was found to be enthalpy-driven above the melting temperature (Tm). A decrease in Tm with PRF content was found whereas the bilayer melting enthalpy ΔHm remains almost constant. The last finding indicates that PRF incorporates into the membrane at a depth near the phosphatidylcholine headgroup, in agreement with our MD-simulations. The simulations also reveal that PRF partitions into the membrane on a timescale of 0.5 μs and has a cholesterol-like ordering effect on DPPC in the fluid phase. The vertical location of the PRF binding site in a bacterial ligand-gated ion channel coincides with the location found in our MD-simulations. Our results suggest that multiple physicochemical mechanisms may determine anesthetic potency of PRF, including effects on proteins that are mediated through the bilayer.

Rod-like polyelectrolyte brushes with mono- and multivalent counterions

A model of rod-like polyelectrolyte brushes in the presence of monovalent and multivalent counterions but with no added salt is studied using Monte Carlo simulation. The average height of the brush, the histogram of rod conformations, and the counterion density profile are obtained for different values of the grafting density of the charge-neutral wall. For a domain of grafting densities, the brush height is found to be relatively insensitive to the density due to a competition between counterion condensation and inter-rod repulsion. In this regime, multivalent counterions collapse the brush in the form of linked clusters. Nematic order emerges at high grafting densities, resulting in an abrupt increase of the brush height.

A general theory of non-equilibrium dynamics of lipid-protein fluid membranes

Abstract.We present a general and systematic theory of non-equilibrium dynamics of multi-component fluid membranes, in general, and membranes containing transmembrane proteins, in particular. Developed based on a minimal number of principles of statistical physics and designed to be a meso/macroscopic-scale effective description, the theory is formulated in terms of a set of equations of hydrodynamics and linear constitutive relations. As a particular emphasis of the theory, the equations and the constitutive relations address both the thermodynamic and the hydrodynamic consequences of the unconventional material characteristics of lipid-protein membranes and contain proposals as well as predictions which have not yet been made in already existing work on membrane hydrodynamics and which may have experimental relevance. The framework structure of the theory makes possible its applications to a range of non-equilibrium phenomena in a range of membrane systems, as discussions in the paper of a few limit cases demonstrate.

Preparing giant unilamellar vesicles (GUVs) of complex lipid mixtures on demand: Mixing small unilamellar vesicles of compositionally heterogeneous mixtures.

Giant unilamellar vesicles (GUVs) are simple model membrane systems of cell-size, which are instrumental to study the function of more complex biological membranes involving heterogeneities in lipid composition, shape, mechanical properties, and chemical properties. We have devised a method that makes it possible to prepare a uniform sample of ternary GUVs of a prescribed composition and heterogeneity by mixing different populations of small unilamellar vesicles (SUVs). The validity of the protocol has been demonstrated by applying it to ternary lipid mixture of DOPC, DPPC, and cholesterol by mixing small unilamellar vesicles (SUVs) of two different populations and with different lipid compositions. The compositional homogeneity among GUVs resulting from SUV mixing is quantified by measuring the area fraction of the liquid ordered-liquid disordered phases in giant vesicles and is found to be comparable to that in GUVs of the prescribed composition produced from hydration of dried lipids mixed in organic solvent. Our method opens up the possibility to quickly increase and manipulate the complexity of GUV membranes in a controlled manner at physiological buffer and temperature conditions. The new protocol will permit quantitative biophysical studies of a whole new class of well-defined model membrane systems of a complexity that resembles biological membranes with rafts.

On a reformulation of the theory of Lifshitz–van der Waals interactions in multilayered systems

In order to investigate the form of the van der Waals interaction in different multilayer geometries we reformulate the Lifshitz theory in terms of an algebra of 2×2 matrices. This device allows us to derive a closed form solution for the secular determinant of the modes in terms of simple quadratures with explicit N dependence. We specifically investigate (i) the van der Waals interactions between a substrate and a multilayer system as a function of the separation between the substrate and the multilayer system and (ii) the interaction between two multilayer systems over a medium of variable separation.