Molecular Dynamics Simulations Showing 1-Palmitoyl-2-Oleoyl-Phosphatidylcholine (POPC) Membrane Mechanoporation Damage under Different Strain Paths

Murphy, M. A., Mun, S., Horstemeyer, M., Baskes, M. I., Bakhtiarydavijani, A., LaPlaca, M. C., Gwaltney, S. R., Williams, L. N., & Prabhu, R. (2018). Molecular Dynamics Simulations Showing 1-Palmitoyl-2-Oleoyl-Phosphatidylcholine (POPC) Membrane Mechanoporation Damage under Different Strain Paths. Journal of Biomolecular Structure & Dynamics. 1-14. DOI:10.1080/07391102.2018.1453376.

Abstract

Continuum finite element material models used for traumatic brain injury lack local injury parameters necessitating nanoscale mechanical injury mechanisms be incorporated. One such mechanism is membrane mechanoporation, which can occur during physical insults and can be devastating to cells, depending on the level of disruption. The current study investigates the strain state dependence of phospholipid bilayer mechanoporation and failure. Using molecular dynamics, a simplified membrane, consisting of 72 1-palmitoyl-2-oleoyl-phosphatidylcholine (POPC) phospholipids, was subjected to equibiaxial, 2:1 non-equibiaxial, 4:1 non-equibiaxial, strip biaxial, and uniaxial tensile deformations at a von Mises strain rate of 5.45 × 10⁸ s⁻¹, resulting in velocities in the range of 1 to 4.6 m·s⁻¹. A water bridge forming through both phospholipid bilayer leaflets was used to determine structural failure. The stress magnitude, failure strain, headgroup clustering, and damage responses were found to be strain state dependent. The strain state order of detrimentality in descending order was equibiaxial, 2:1 nonequibiaxial, 4:1 non-equibiaxial, strip biaxial, and uniaxial. The phospholipid bilayer failed at von Mises strains of 0.46, 0.47, 0.53, 0.77, and 1.67 during these respective strain path simulations. Additionally, a Membrane Failure Limit Diagram (MFLD) was created using the pore nucleation, growth, and failure strains to demonstrate safe and unsafe membrane deformation regions. This MFLD allowed representative equations to be derived to predict membrane failure from in-plane strains. These results provide the basis to implement a more accurate mechano-physiological internal state variable continuum model that captures lower length scale damage and will aid in developing higher fidelity injury models.