Tortuosity in the Brick and Mortar Model Based on Chemical Conduction

Diffusion is a reoccurring phenomena in many fields and is affected by the geometry in which it takes place. Here we investigate the effects of geometry on diffusion in a Brick and Mortar model system. The tortuous effects are evaluated based on generalized Fick's law, i.e. diffusion driven by differences in chemical potential. The presented formalism gives a general (semi-)exact analytic expression for the tortuosity using impermeable Bricks, which is successfully validated against standard techniques and finite element method results. The approach allows for anisotropic properties of the Mortar, which we show can be significant and is not captured with known analytic techniques. Based on the introduced concept of chemical conductivity we also find generalized Fick's law consistent with Ohm's and Fourier's law in terms of their constituent parts, which further makes the main results for brick and mortar structures directly applicable to diffusion of either charge, heat, or mass

Drying aqueous colloidal systems: Molecular interactions, self-assembly and homeostatic behavior

Evaporation is a ubiquitous process in aqueous systems, which may be advantageous for processing materials through drying or deadly for living systems. Since surfactants, polymers and particles are usually non-volatile, water evaporation will lead to the build-up of concentration gradients in the system, from the air/liquid interface into the dispersion’s bulk. These concentration gradients will in turn generate structuration gradients in the colloidal system, which lead to changes in transport properties along the gradients. We will show that such a feedback loop on water evaporation can lead to non-linear behaviors, which are crucial for land-living animals’ survival and opens new avenues in drying and filtration processes. We designed millifluidic drying cells, which consist of a small capillary attached to a large reservoir, with one tip exposed to air at a controlled relative humidity. Chemical potential boundary conditions are thus set and controlled during drying. We monitored drying with time with a combination of mapping techniques: polarized microscopy, infra-red microscopy and coherent small-angle scattering, which yields both concentration and structuration gradients. We also measured independently the evaporation rate through gravimetry. Using simple surfactant aqueous solutions, we show that the evaporation rate is nearly independent of water evaporation driving force, the air relative humidity [1]. Strikingly, this behavior is identical to that of stratum corneum, skin’s outer layer. We demonstrate that this non-linear behavior stems from the feedback loop on water transport. Dryer air should lead to a higher evaporation rate due to an increased chemical potential difference between the air and the solution. However, this variation is absorbed in a very thin and dry phase at the air/water interface. This phase corresponds to dramatically low water diffusion coefficients, which in turn efficiently decrease water evaporation [2]. Uncovering the mechanism of this homeostatic behavior opens new strategies to evaluate the impact of a formulation on skin, lung or tear films. We will also show that this mechanism becomes relevant when drying, or filtering, dispersions of interpenetrable colloids, such as microgels or “hairy” particles [3]. Indeed, large changes in water chemical potential and permeabilities will occur in the concentrated regime, in contrast to the drying of more conventional colloidal dispersions. Taking these molecular interactions into account is crucial for the processing of more complex, and thus realistic, colloidal dispersions into materials. Please click Additional Files below to see the full abstract

Influence of polar co-solutes and salt on the hydration of lipid membranes

The influence of the co-solutes TMAO, urea, and NaCl on the hydration repulsion between lipid membranes is investigated in a combined experimental/simulation approach. Pressure–hydration curves obtained via sorption experiments reveal that the repulsion significantly increases when the membranes are loaded with co-solutes, most strongly for TMAO. As a result, the co-solutes retain additional water molecules and therefore provide membranes with a fluid and more physiological environment. The experimental data are quantitatively reproduced in complementary solvent-explicit atomistic molecular dynamics simulations, which yield the chemical potential of water. Simulation analysis reveals that the additional repulsion arises from the osmotic pressure generated by the co-solutes, an effect which is maximal for TMAO, due to its unfavorable interactions with the lipid headgroup layer and its extraordinarily high osmotic coefficient

RNA and DNA interactions with zwitterionic and charged lipid membranes — A DSC and QCM-D study

AbstractThe aim of the present study is to establish under which conditions tRNA associates with phospholipid bilayers, and to explore how this interaction influences the lipid bilayer. For this purpose we have studied the association of tRNA or DNA of different sizes and degrees of base pairing with a set of model membrane systems with varying charge densities, composed of zwitterionic phosphatidylcholines (PC) in mixtures with anionic phosphatidylserine (PS) or cationic dioctadecyl-dimethyl-ammoniumbromide (DODAB), and with fluid or solid acyl-chains (oleoyl, myristoyl and palmitoyl). To prove and quantify the attractive interaction between tRNA and model-lipid membrane we used quartz crystal microbalance with dissipation (QCM-D) monitoring to study the tRNA adsorption to deposit phospholipid bilayers from solutions containing monovalent (Na+) or divalent (Ca2+) cations. The influence of the adsorbed polynucleic acids on the lipid phase transitions and lipid segregation was studied by means of differential scanning calorimetry (DSC). The basic findings are: i) tRNA adsorbs to zwitterionic liquid-crystalline and gel-phase phospholipid bilayers. The interaction is weak and reversible, and cannot be explained only on the basis of electrostatic attraction. ii) The adsorbed amount of tRNA is higher for liquid-crystalline bilayers compared to gel-phase bilayers, while the presence of divalent cations show no significant effect on the tRNA adsorption. iii) The adsorption of tRNA can lead to segregation in the mixed 1,2-dimyristoyl-sn-glycerol-3-phosphatidylcholine (DMPC)-1,2-dimyristoyl-sn-glycero-3-phosphatidylserine (DMPS) and DMPC–DODAB bilayers, where tRNA is likely excluded from the anionic DMPS-rich domains in the first system, and associated with the cationic DODAB-rich domains in the second system. iv) The addition of shorter polynucleic acids influence the chain melting transition and induce segregation in a mixed DMPC–DMPS system, while larger polynucleic acids do not influence the melting transition in these system. The results in this study on tRNA–phospholipid interactions can have implications for understanding its biological function in, e.g., the cell nuclei, as well as in applications in biotechnology and medicine

How Small Polar Molecules Protect Membrane Systems against Osmotic Stress: The Urea−Water−Phospholipid System

We investigate how a small polar molecule, urea, can act to protect a phospholipid bilayer system against osmotic stress. Osmotic stress can be caused by a dry environment, by freezing, or by exposure to aqueous systems with high osmotic pressure due to solutes like in saline water. A large number of organisms regularly experience osmotic stress, and it is a common response to produce small polar molecules intracellularly. We have selected a ternary system of urea-water-dimyristoyl phosphatidylcholine (DMPC) as a model to investigate the molecular mechanism behind this protective effect, in this case, of urea, and we put special emphasis on the applications of urea in skin care products. Using differential scanning calorimetry, X-ray diffraction, and sorption microbalance measurements, we studied the phase behavior of lipid systems exposed to an excess of solvent of varying compositions, as well as lipid systems exposed to water at reduced relative humidities. From this, we have arrived at a rather detailed thermodynamic characterization. The basic findings are as follows: (i) In excess solvent, the thermally induced lipid phase transitions are only marginally dependent on the urea content, with the exception being that the P phase is not observed in the presence of urea. (ii) For lipid systems with limited access to solvent, the phase behavior is basically determined by the amount (volume) of solvent irrespective of the urea content. (iii) The presence of urea has the effect of retaining the liquid crystalline phase at relative humidities down to 64% (at 27 °C), whereas, in the absence of urea, the transition to the gel phase occurs already at a relative humidity of 94%. This demonstrates the protective effect of urea against osmotic stress. (iv) In skin care products, urea is referred to as a moisturizer, which we find slightly misleading as it replaces the water while keeping the physical properties unaltered. (v) In other systems, urea is known to weaken the hydrophobic interactions, while for the lipid system we find few signs of this loosening of the strong segregation into polar and apolar regions on addition of ure

Membrane Interaction of α-Synuclein in Different Aggregation States

Aggregated α-synuclein in Lewy bodies is one of the hallmarks of Parkinson's disease (PD). Earlier observations of α-synuclein aggregates in neurons grafted into brains of PD patients suggested cell-to-cell transfer of α-synuclein and a prion-like mechanism. This prompted the current investigation of whether α-synuclein passes over model phospholipid bilayers. We generated giant unilamellar vesicles (GUVs) containing a small amount of a lipid-conjugated red emitting dye (rhodamine B) and varied the membrane charge by using different molar ratios of DOPC and DOPS or cardiolipin. We then used confocal fluorescence microscopy to examine how monomer, fibril as well as on-pathway α-synuclein species labeled with a green emitting fluorophore (Alexa488) interacted with the phospholipid bilayers of the GUV. We defined conditions that yielded reproducible aggregation kinetics under basal conditions and with none or moderate shaking. We found that on-pathway α-synuclein species and equilibrium amyloid aggregates, but not α-synuclein monomers, bound to lipid membranes. α-Synuclein was particularly strongly associated with GUVs containing the anionic lipids cardiolipin or DOPS, whereas it did not associate with GUVs containing only zwitterionic DOPC. We found that α-synuclein progressively aggregated at the surface of the GUVs, typically in distinct domains rather than uniformly covering the membrane, and that both lipid and protein were incorporated in the aggregates. Importantly, we never observed transport of α-synuclein over the GUV bilayer. This suggests that α-synuclein transport over membranes requires additional molecular players and that it might rely on active transport

Drug Transport in Responding Lipid Membranes Can Be Regulated by an External Osmotic Gradient

In this paper, we demonstrate, for the first time, how an external osmotic gradient can be used to regulate diffusion of solutes across a lipid membrane. We present experimental and theoretical studies of the transport of different solutes across a monoolein membrane in the presence of an external osmotic gradient. The osmotic gradient introduces phase transformations in the membrane, and it causes nonlinear transport behavior. The external gradient can thus act as a kind of switch for diffusive transport in the skin and in controlled release drug formulations

Controlling water evaporation through self-assembly

Water evaporation concerns all land-living organisms, as ambient air is dryer than their corresponding equilibrium humidity. Contrarily to plants, mammals are covered with a skin that not only hinders evaporation but also maintains its rate at a nearly constant value, independently of air humidity. Here, we show that simple amphiphiles/water systems reproduce this behavior, which suggests a common underlying mechanism originating from responding self-assembly structures. The composition and structure gradients arising from the evaporation process were characterized using optical microscopy, infrared microscopy, and small-angle X-ray scattering. We observed a thin and dry outer phase that responds to changes in air humidity by increasing its thickness as the air becomes dryer, which decreases its permeability to water, thus counterbalancing the increase in the evaporation driving force. This thin and dry outer phase therefore shields the systems from humidity variations. Such a feedback loop achieves a homeostatic regulation of water evaporation

Cholesterol catalyses Aβ42 aggregation through a heterogeneous nucleation pathway in the presence of lipid membranes.

Alzheimer's disease is a neurodegenerative disorder associated with the aberrant aggregation of the amyloid-β peptide. Although increasing evidence implicates cholesterol in the pathogenesis of Alzheimer's disease, the detailed mechanistic link between this lipid molecule and the disease process remains to be fully established. To address this problem, we adopt a kinetics-based strategy that reveals a specific catalytic role of cholesterol in the aggregation of Aβ42 (the 42-residue form of the amyloid-β peptide). More specifically, we demonstrate that lipid membranes containing cholesterol promote Aβ42 aggregation by enhancing its primary nucleation rate by up to 20-fold through a heterogeneous nucleation pathway. We further show that this process occurs as a result of cooperativity in the interaction of multiple cholesterol molecules with Aβ42. These results identify a specific microscopic pathway by which cholesterol dramatically enhances the onset of Aβ42 aggregation, thereby helping rationalize the link between Alzheimer's disease and the impairment of cholesterol homeostasis