Permeability of membranes in the liquid ordered and liquid disordered phases

Abstract

The functional significance of ordered nanodomains (or rafts) in cholesterol rich eukaryotic cell membranes has only begun to be explored. This study exploits the correspondence of cellular rafts and liquid ordered (Lo) phases of three-component lipid bilayers to examine permeability. Molecular dynamics simulations of Lo phase dipalmitoylphosphatidylcholine (DPPC), dioleoylphosphatidylcholine (DOPC), and cholesterol show that oxygen and water transit a leaflet through the DOPC and cholesterol rich boundaries of hexagonally packed DPPC microdomains, freely diffuse along the bilayer midplane, and escape the membrane along the boundary regions. Electron paramagnetic resonance experiments provide critical validation: the measured ratio of oxygen concentrations near the midplanes of liquid disordered (Ld) and Lo bilayers of DPPC/DOPC/cholesterol is 1.75 ± 0.35, in very good agreement with 1.3 ± 0.3 obtained from simulation. The results show how cellular rafts can be structurally rigid signaling platforms while remaining nearly as permeable to small molecules as the Ld phase.

Beyond Shielding: The Roles of Glycans in SARS-CoV-2 Spike Protein

“…These results are in agreement with known POPC and previously reported binary POPC + X trends, where X is any other lipid added to the mix. [46][47][48][49][50][51][52]…”

Molecular Dynamics Simulations of Membrane Permeability

“…The next step in understanding permeability within the context of a diffusion model is to allow for variation of diffusion constant and free energy of the membrane interior, which leads to the inhomogeneous solubility diffusion (ISD) model. This is done through the Smoluchowski equation in one-dimension: 27 ∂ p ∂t = ∂ ∂z D ⊥ z e −βF z ∂ ∂z e βF z p (13) where D ⊥ z and F z are the diffusion and free energy profiles respectively along the bilayer normal, β = 1/k B T, and k B is Boltzmann's constant. Eq.…”

“…8 bottom) and oxygen. 13 However, for less soluble permeants it may be more efficient (or necessary) to obtain F z from umbrella sampling [109][110][111] (where the particle is restrained to a particular z, and the PMF is assembled from the distributions at different z). ΔG w h may also be obtained from more advanced free energy methods.…”

“…Section 5 also reviews an extension of the Smoluchowski equation to include lateral diffusion of permeants in the membrane and a Bayesian analysis (BA) method to extract diffusion tensors from trajectories. [13][14] Sections 6 and 7 test approaches based on Fick's Law and the ISD equation for water and oxygen using simulations of 12 and 7 different bilayers, respectively. Effects of undulations (Section 6.1), periodic boundary conditions (6.2), the validity of the ISD model (Section 7.1), and agreement with experiment (7.2) are considered.…”

Bioinspired nano-ordered liquid membrane for precise molecular separation

“…39,40 Therefore, ILs are anticipated to be a novel and leading candidate for developing bioinspired membranes with transport nanochannels. 41,42 Herein, we present, from inception to implementation, a family of bioinspired nanoordered liquid membranes with excellent separation performance for ethylene/ethane (0.416 nm / 0.443 nm) separation, 43 which are constructed from ion/molecule self-assembly of protic salts (PSs, solid protic ionic liquids at room temperature), polyol and ethylene-transport carrier (AgNO 3 ), where the PSs imitate phospholipid molecules, and the combination of polyol and AgNO 3 carrier imitates carrier protein. The regulation of hydrogen bonding, electrostatic and amphiphilicity interactions by optimizing their compositions can confer the nano-ordered liquid structure with interpenetrating and continuous apolar domains and polar domains, which results in the formation of regular carrier wires and enormous 3D interconnected ethylene transport nanochannels.…”