# Studying the Effects of Dissolved Noble Gases and High Hydrostatic Pressure on the Spherical DOPC Bilayer Using Molecular Dynamic Simulations

## TL;DR

This study uses simulations to explore how noble gases and high pressure affect lipid membranes, shedding light on neurological effects in deep-sea divers.

## Contribution

The study introduces a refined method to differentiate the effects of noble gases from high pressure on lipid bilayers using molecular dynamics.

## Key findings

- Xenon, argon, and neon form nanobubbles that distort lipid membranes, supporting the multisite distortion hypothesis.
- Hyperbaric helium causes minimal membrane distortion without forming condensed gas fractions in the hydrophobic core.
- Noble gas bubbles are distributed across both solvent and lipid phases, leading to significant membrane deformation.

## Abstract

Fine-grained molecular dynamics simulations have been conducted to depict lipid objects enclosed in water and interacting with a series of noble gases dissolved in the medium. The simple point-charge (SPC) water system, featuring a boundary composed of 1,2-Dioleoyl-sn-glycero-3-phosphocholine (DOPC) molecules, maintained stability throughout the simulation under standard conditions. This allowed for the accurate modeling of the effects of hydrostatic pressure at an ambient pressure of 25 bar. The chosen pressure references the 240 m depth of seawater: the horizon frequently used by commercial divers, who comprise the primary patient population of the neurological complication of inert gas narcosis and the consequences of high-pressure neurological syndrome. To quantify and validate the neurological effects of noble gases and discriminate them from high hydrostatic pressure, we reduced the dissolved gas molar concentration to 1.5%, three times smaller than what we previously tested for the planar bilayer (3.5%). The nucleation and growth of xenon, argon and neon nanobubbles proved consistent with the data from the planar bilayer simulations. On the other hand, hyperbaric helium induces only a residual distorting effect on the liposome, with no significant condensed gas fraction observed within the hydrophobic core. The bubbles were distributed over a large volume—both in the bulk solvent and in the lipid phase—thereby causing substantial membrane distortion. This finding serves as evidence of the validity of the multisite distortion hypothesis for the neurological effect of inert gases at high pressure.