Electroporation Using Dissipative Particle Dynamics with a Novel Protocol for Applying Electric Field

摘要

In molecular dynamics simulations of membrane electroporation, the bilayer is subjected to an electric field E either by direct addition of a force f = qE on the charge-bearing species or by imposing an ion imbalance in the salt solutions on the two sides of the bilayer. The former is believed to mimic electroporation with high fields over nanosecond pulse period, during which the membrane is almost uncharged, especially in the low salt limit. Conversely, the ion imbalance method elucidates a low electric field-induced poration over a longer period of micro- to milliseconds with a fully charged membrane. Both these methods of applying electric field have disadvantages while investigating electroporation using dissipative particle dynamics (DPD) simulations. The method involving direct addition of force fails to address the presence of a nonuniform dielectric background for ions embedded in nonpolarizable DPD water and those found in the core of the bilayer. The ion imbalance method in DPD simulations suffers from its unavoidable use of a wall potential to prevent the movement of ions across the periodic boundaries. To address the above issues, we propose a simple method for imposing a desired transmembrane potential (TMV) by placing oppositely but uniformly charged plates on either side of the bilayer. Our DPD simulations demonstrate that the profiles for bead density, mechanical stress, electrical potential, as well as the transient responses in the dipole moment and species fluxes obtained from the proposed method utilizing charged plates are quite similar to those obtained using the ion imbalance method. The proposed protocol is free from the aforementioned drawbacks of the direct force addition and ion imbalance methods.