Phospholipid Bilayer Recovery Response Following In-Plane Biaxial Deformations

INTRODUCTION

Despite affecting an estimated 10 million people every year and resulting in enormous financial and personal loss, the nanoscale effects of traumatic brain injury (TBI) are not well understood. This information is often missing from finite element models, which must implement lower length scale information through constitutive material models to more accurately replicate the brain’s response to TBI. One important lower length scale mechanism leading to TBI is membrane mechanoporation. Studies have previously explored the stress-strain response of simplified membranes at differing strain rates and strain states using molecular dynamics. However, these studies did not examine what occurs to the membrane post-deformation. Therefore, the current study examines the recovery behavior of simplified cellular membrane systems after they have been deformed biaxially. This work provides important insights into the recovery of cellular membranes following mechanical insult perturbation, as occurs during traumatic brain injury due to mechanoporation.

METHODS

Seventy-two 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) phospholipids and 9,070 TIP3P water molecules (original structure sourced from NIH’s Laboratory of Computation Library and 6,828 TIP3P water molecules were added) were equilibrated for ten nanoseconds using the program LAMMPS and the CHARMM36 all-atom lipid force field. The equilibrated structure was subjected to constant velocity tensile deformations in the x and y (in-plane) dimensions to simulate the equibiaxial, 2:1 non-equibiaxial, 4:1 non-equibiaxial, strip biaxial, and uniaxial strain states. X and y strain rates were determined so that all strain states had a von Mises strain rate of 5.5 × 10⁸ s^-1. The out-of-plane (z) dimension could relax freely during deformations.

After deforming the phospholipid bilayer, structure snapshots corresponding to pre-yield, yield, post-yield, the first pore large enough for water penetration (determined via image analysis), and failure (assumed to occur when a chain of water fully penetrated the bilayer through both bilayer leaflets) were determined. These structures were then relaxed using the isothermal-isobaric (NPT) ensemble. These relaxed structures were compared to the pre-deformed structures to determine any permanent structure changes.

Preliminary Results and conclusions

When allowed to relax, the phospholipid bilayer’s planar area quickly reduced to a value much smaller than the deformed state. However, the relaxed structure planar area depended on how far the phospholipid bilayer structure was deformed. Specifically, the deformed-structure snapshots taken prior to yield relaxed to a planar area similar to the non-deformed, equilibrated structures. However, snapshots taken at yield and post-yield demonstrated increasingly larger planar areas compared to the non-deformed, equilibrated structures. This permanent change in planar area (under the time scales examined) for only snapshots taken at yield and later time points indicates that plastic deformation effects have occurred for the structure.