Modelling of noble anaesthetic gases and high hydrostatic pressure effects in lipid bilayers

Abstract

Our objective was to study molecular processes that might be responsible for inert gas narcosis and high-pressure nervous syndrome. The classical molecular dynamics trajectories (200 ns) of dioleoylphosphatidylcholine (DOPC) bilayers simulated by the Berger force field were evaluated for water and the atomic distribution of noble gases around DOPC molecules in the pressure range of 1-1000 bar and at a temperature of 310 K. Xenon and argon have been tested as model gases for general anaesthetics, and neon has been investigated for distortions that are potentially responsible for neurological tremors in hyperbaric conditions. The analysis of stacked radial pair distribution functions of DOPC headgroup atoms revealed the explicit solvation potential of the gas molecules, which correlates with their dimensions. The orientational dynamics of water molecules at the biomolecular interface should be considered as an influential factor, while excessive solvation effects appearing in the lumen of membrane-embedded ion channels could be a possible cause of inert gas narcosis. All the noble gases tested exhibit similar order parameter patterns for both DOPC acyl chains, which are opposite of the patterns found for the order parameter curve at high hydrostatic pressures in intact bilayers. This finding supports the 'critical volume' hypothesis of anaesthesia pressure reversal. The irregular lipid headgroup-water boundary observed in DOPC bilayers saturated with neon in the pressure range of 1-100 bar could be associated with the possible manifestation of neurological tremors at the atomic scale. The non-immobiliser neon also demonstrated the highest momentum impact on the normal component of the DOPC diffusion coefficient representing the monolayer undulation rate, which indicates that enhanced diffusivity rather than atomic size is the key factor.

Molecular Dynamics Simulation for Mechanism Elucidation of Food Processing and Safety: State of the Art

“…For instance, the study of a multicomponent chocolate system opened a new way for using MD simulation in complex soft matter foods (Greiner et al, 2014). Apart from above achievements, the effects of pressure and electric field on lipid membrane are also studied through MD simulations, which may help unveiling the underlying processing mechanism for food safety (Ding, Palaiokostas, Shahane, Wang, & Orsi, 2017;Moskovitz & Yang, 2015;Tao et al, 2014).…”

“…Theoretical studies to reveal the related mechanism have been applied and achieved some advances through MD simulations. The stacked radial pair distribution functions of dioleoylphosphatidylcholine (DOPC) head group atoms may impose a potential barrier on the anesthetic gas atoms (Moskovitz & Yang, ). It was observed that the lipid–solvent boundary was deformed by neon at moderate pressure of 10 MPa, implying significant breakage of the lipid head group planar arrangement.…”

The cellular membrane as a mediator for small molecule interaction with membrane proteins

“…Although the simulation of simple gases also applies to the study of general anesthetics (GAs), such as for xenon [121–125] which is both a gas and a known anesthetic, the simulation of other structuraly complex GAs in the membrane environment introduces additional obstacles and complexity. The need for de novo parametrization, together with the additional degrees of freedom available to GAs, allows for more diverse and complex interactions with membrane lipids and associated proteins.…”

Lateral Pressure Profile and Free Volume Properties in Phospholipid Membranes Containing Anesthetics

“…11,12,14 In some other studies the fluidity of the membrane was thought to be the relevant property in this respect. 15,16 Although a number of experimental 11,12,15,16 and computer simulation studies [17][18][19][20] provided results that are consistent with the above hypotheses, other studies found these properties to be insensitive to the presence of anesthetics, [21][22][23][24][25] or even provided results contradicting some of these assumptions. [26][27][28][29] This controversy of the existing results largely originates from the fact that different anesthetics as well as membranes of different compositions have been considered in the different studies.…”