Anomalous viscosity effect in the early stages of the ion-assisted adhesion/fusion event between lipid bilayers: A theoretical and computational study

Abstract

The effect of viscosity on the encounter rate of two interacting membranes was investigated by combining a non-equilibrium Fokker-Planck model together with extensive Molecular Dynamics (MD) calculations. The encounter probability and stabilization of transient contact points represent the preliminary steps toward short-range adhesion and fusion of lipid leaflets. To strengthen our analytical model, we used a Coarse Grained MD method to follow the behavior of two charged palmitoyl oleoyl phosphatidylglycerol membranes embedded in a electrolyte-containing box at different viscosity regimes. Solvent friction was modulated by varying the concentration of a neutral, watersoluble polymer, polyethylene glycol, while contact points were stabilized by divalent ions that form bridges among juxtaposed membranes. While a naïve picture foresees a monotonous decrease of the membranes encounter rate with solvent viscosity, both the analytical model and MD simulations show a complex behavior. Under particular conditions, the encounter rate could exhibit a maximum at a critical viscosity value or for a critical concentration of bridging ions. These results seem to be confirmed by experimental observations taken from the literature. © 2013 AIP Publishing LLC.

Simulation of polyethylene glycol and calcium-mediated membrane fusion

“…Based on the current data and our previous findings, 8,26,27 we propose a multiple stage mechanism for PEG/Ca 2+ mediated fusion, starting from bilayer approach, via adhesion, to stalk formation. Each of these steps is discussed in the following.…”

Methodologies for the analysis of instantaneous lipid diffusion in md simulations of large membrane systems

“…This module was previously employed to calculate lipid diffusion coefficient 43,44 using the Einstein relation. “Restart” parameters of 2 ns and 5 ns were compared to measure their influence on the MSD curve and diffusion coefficient.…”

“…The mean square deviation (MSD) was calculated using the g_msd module in the GROMACS 4.5.4 package. 37,42 This module was previously employed to calculate lipid diffusion coefficient 43,44 using the Einstein relation. "Restart" parameters of 2 ns and 5 ns were compared to measure their inuence on the MSD curve and diffusion coefficient.…”

Hydrodynamic Enhancement of the Diffusion Rate in the Region between Two Fluctuating Membranes in Close Opposition: A Theoretical and Computational Study

“…This goal is easily reached by using polymer chains soluble in the water phase. It is known that polymers are excluded from the narrow gap between bodies in close opposition by a combination of steric and dielectric effects. , Because of polymer exclusion from the intermembrane gap, the diffusant mobility does not depend on polymer amount. On the contrary, the external viscosity dramatically increases, especially in the case of long polymer chains. , Solvent viscosity strongly damps the oscillation rates of juxtaposed plates.…”

“…In pure water, μ water = 10 –3 N·s·m –2 , but much higher values, strongly depending on the experimental technique and related to the size of the moving particle, have been measured in polymeric solutions or in the cytoplasm . It must be borne in mind that in polymeric solvents the viscosity felt by the diffusant and that experienced by a mesoscopic fluctuating body can be markedly different: usually diffusant is much smaller than the polymer gyration radius, so its motion is not significantly affected by the polymer chains . On the contrary, the fluctuating body (e.g., a vesicle or cell) is much larger than the polymeric coil size; then friction effects are expected to be huge and related to chains length and concentration. , Hence, by relating the mass M with the spherical cell radius scriptR and density δ we find γ ∝ M –7/9 ≈ 10 7 s –1 .…”