Hypothesis: Sphingomyelin (SPM), a crucial phospholipid in the myelin sheath, is vital in insulating nerve fibers. We hypothesize that iron ions selectively bind to the phosphatidylcholine (PC) template within the SPM membrane under near-physiological conditions, disrupting membrane organization. These interactions could potentially contribute to the degradation of the myelin sheath, thereby playing a role in the development of neurodegenerative diseases. Experiments: We utilized synchrotron-based X-ray spectroscopy and diffraction techniques to study the interaction of iron ions with a bovine spinal cord SPM monolayer (ML) at the liquid-vapor interface under physiological conditions. The SPM ML serves as a model system, representing localized patches of lipids within a more complex membrane structure. The experiments assessed iron binding to the SPM membrane both in the presence of salts and with additional evaluation of the effects of various ion species on membrane behavior. Grazing incidence X-ray diffraction was employed to analyze the impact of iron binding on the structural integrity of the SPM membrane. Findings: Our results demonstrate that iron ions in dilute solution selectively bind to the PC template of the SPM membrane exclusively at near-physiological salt concentrations (e.g., NaCl, KCl, KI, or CaCl2) and are pH-dependent. In-significant binding was detected without these salts or at near-neutral pH with salts. The surface adsorption of iron ions is correlated with salt concentration, reaching saturation at physiological levels. In contrast, multivalent ions such as La$^{3+}$ and Ca2+ do not bind to SPM under similar conditions. Notably, iron binding to the SPM membrane disrupts its in-plane organization, suggesting that these interactions may compromise membrane integrity and contribute to myelin sheath damage associated with neurological disorders.
Doxorubicin (DOX) is one of the most efficient antitumor drugs employed in numerous cancer therapies. Its incorporation into lipid-based nanocarriers, such as liposomes, improves the drug targeting into tumor cells and reduces drug side effects. The carriers' lipid composition is expected to affect the interactions of DOX and its partitioning into liposomal membranes. To get a rational insight into this aspect and determine promising lipid compositions, we use numerical simulations, which provide unique information on DOX-membrane interactions at the atomic level of resolution. In particular, …
Polymer membranes are typically assumed to be inert and nonresponsive to the flux and density of the permeating particles in transport processes. Here, we study theoretically the consequences of membrane responsiveness and feedback on the steady-state force--flux relations and membrane permeability using a nonlinear-feedback solution-diffusion model of transport through a slab-like membrane. Therein, the solute concentration inside the membrane depends on the bulk concentration, $c_0$, the driving force, $f$, and the polymer volume fraction, $ϕ$. In our model, solute accumulation in the membra…
We develop a multiscale simulation model for diffusion of solutes through porous triblock copolymer membranes. The approach combines two techniques: self-consistent field theory (SCFT) to predict the structure of the self-assembled, solvated membrane and on-lattice kinetic Monte Carlo (kMC) simulations to model diffusion of solutes. Solvation is simulated in SCFT by constraining the glassy membrane matrix while relaxing the brush-like membrane pore coating against the solvent. The kMC simulations capture the resulting solute spatial distribution and concentration-dependent local diffusivity in…
The Angstrom-scale transport characteristics of water and six different solutes, methanol, ethanol, 2-propanol, urea, Na+, and Cl-, were studied for a polyamide reverse osmosis (RO) membrane, FT-30, using non-equilibrium molecular dynamics (NEMD) simulations. Results indicate that water transport increases with an increasing fraction of connected percolated free volume, or water-accessible open space, in the membrane polymer structure. This free volume is enhanced by the dynamic structure of the membrane at the molecular level as it swells when hydrated and vibrates due to molecular collisions…
Despite the success of reverse osmosis (RO) for water purification, the molecular-level physico-chemical processes of contaminant rejection are not well understood. Here we carry out NEMD simulations on a model polyamide RO membrane to understand the mechanisms of transport and rejection of both ionic and neutral contaminants in water. We observe that the rejection changes non-monotonously with ion sizes. In particular, the rejection of urea, 2.4 A radius, is higher than ethanol, 2.6 A radius, and the rejections for organic solutes, 2.2-2.8 A radius, are lower than Na+, 1.4 A radius, or Cl-, 2…
Transport of liquid mixtures through porous membranes is central to processes such as desalination, chemical separations and energy harvesting, with ultrathin membranes made from novel 2D nanomaterials showing exceptional promise. Here we derive, for the first time, general equations for the solution and solute fluxes through a circular pore in an ultrathin planar membrane induced by a solute concentration gradient. We show that the equations accurately capture the fluid fluxes measured in finite-element numerical simulations for weak solute-membrane interactions. We also derive scaling laws f…
The determination of potentials of mean force for solute insertion in a membrane by means of all-atom molecular dynamics simulations is often hampered by sampling issues. A multiscale approach to conformational sampling was recently proposed by Bereau and Kremer (2016). It aims at accelerating the sampling of the atomistic conformational space by means of a systematic backmapping of coarse-grained snapshots. In this work, we first analyze the efficiency of this method by comparing its predictions for propanol insertion into a 1,2-Dimyristoyl-sn-glycero-3-phosphocholine membrane (DMPC) against …
To overcome the traditional paradigm of filtration, where separation is essentially performed upon steric sieving principles, we explore the concept of dynamic osmosis through active membranes. A partially permeable membrane presents a time-tuneable feature that changes the effective pore interaction with the solute and thus actively changes permeability with time. In general we find that slow flickering frequencies effectively decrease the osmotic pressure, and large flickering frequencies do not change it. In the presence of an asymmetric membrane, we find a resonant frequency where pumping …
Mathematically modeling complex transport phenomena at the molecular level can be a powerful tool for identifying transport mechanisms and predicting macroscopic properties. We use two different stochastic time series models, parameterized from long molecular dynamics (MD) simulation trajectories of a cross-linked HII phase lyotropic liquid crystal (LLC) membrane, in order to predict solute mean squared displacements (MSDs) and solute flux, and thus solute selectivity, in macroscopic length pores. First, using anomalous diffusion theory, we show how solute dynamics can be modeled as a fraction…
The ability of semipermeable membranes to selectively impede the transport of undesirable solutes is key to many applications. Yet, obtaining a systematic understanding of how membrane structure affects selectivity remains elusive due to the insufficient spatiotemporal resolution of existing experimental techniques, and the inaccessibility of relevant solute transport timescales to conventional molecular simulations. Here, we utilize jumpy forward-flux sampling to probe the transport of sodium and chloride ions through a graphitic membrane with sub-nm pores. We find chlorides to traverse the p…
Osmotically Induced Shape Changes in Membrane Vesicles
Kansas State University（堪萨斯州立大学）；NewOrbit Space Ltd（NewOrbit空间有限公司）；University of Sheffield（谢菲尔德大学）；Kaplan International College（凯伦国际学院）；Université Paris-Saclay（巴黎萨克雷大学）
In this paper, we explore osmotic transport by means of molecular dynamics (MD) simulations. We first consider osmosis through a membrane, and investigate the reflection coefficient of an imperfectly semi-permeable membrane, in the dilute and high concentration regimes. We then explore the diffusion-osmotic flow of a solute-solvent fluid adjacent to a solid surface, driven by a chemical potential gradient parallel to the surface. We propose a novel non-equilibrium MD (NEMD) methodology to simulate diffusion-osmosis, by imposing an external force on every particle, which properly mimics the che…
Modern biomedical applications such as targeted drug delivery require a delivery system capable of enhanced transport beyond that of passive Brownian diffusion. In this work an osmotic mechanism for the propulsion of a vesicle immersed in a viscous fluid is proposed. By maintaining a steady-state solute gradient inside the vesicle, a seepage flow of the solvent (e.g., water) across the semipermeable membrane is generated which in turn propels the vesicle. We develop a theoretical model for this vesicle-solute system in which the seepage flow is described by a Darcy flow. Using the reciprocal t…
We examine theoretically porous membranes in aqueous mixtures. We show that large membrane pores can be reversibly gated from `off' (co-solvent-rich, poor conductor of ions and other solutes) to 'on' (water-rich, good conductor) states by an external potential. The transition voltage or charge for switching depends on the membrane hydrophilicity/hydrophobicity, the salt content, the preferential solvation of the salt ions, and the temperature. These parameters also determine whether the filling transition is abrupt or gradual.
As solute molecules permeate into a vesicle due to a concentration difference across its membrane, the vesicle swells through osmosis. The swelling can be divided into two stages: (a) an "ironing" stage, where the volume-to-area ratio of the vesicle increases without a significant change in its area; (b) a stretching stage, where the vesicle grows while remaining essentially spherical, until it ruptures. We show that the crossover between these two stages can be represented as a broadened continuous phase transition. Consequently, the swelling curves for different vesicles and different permea…
There has been intense interest in filtration and separation properties of graphene-based materials that can have well-defined nanometer pores and exhibit low frictional water flow inside them. Here we investigate molecular permeation through graphene oxide laminates. They are vacuum-tight in the dry state but, if immersed in water, act as molecular sieves blocking all solutes with hydrated radii larger than 4.5A. Smaller ions permeate through the membranes with little impedance, many orders of magnitude faster than the diffusion mechanism can account for. We explain this behavior by a network…
An algorithm is proposed to implement unsteady jump boundary conditions, presenting discontinuity in physical quantities, within the lattice Boltzmann method (LBM). This is useful to tackle problems involving mass or heat transfer through interfaces or membranes that exhibit resistance to transport. The algorithm is simple to implement within an existing LBM based code that computes diffusion and advection of a scalar field, either temperature or solute concentration. Analytical solutions are recovered numerically with acceptable accuracy for the limiting case of a planar membrane. The algorit…
Accounting for concentration-polarization (CP) is critical for modeling solute transport in membrane separation processes. In a mixed-electrolyte solution, ions CP is affected not only by diffusion and advection but also by electromigration. Yet, the classic film model, lacking an electromigration term, is frequently used for modeling ion CP. Often, ion CP is altogether neglected to reduce the computational load. Here, we study the CP of trace ions in a dominant salt solution, a case relevant for many reverse-osmosis and nanofiltration processes. First, we revisit the solution-diffusion-electr…
