Molecular dynamics simulation of reversible electroporation with Martini force field

Abstract

BackgroundAfter the discovery of membrane-reversible electroporation decades ago, the procedure has been used extensively in biology, biotechnology and medicine. The research on the basic mechanism has increasingly attracted attention. Although most research has focused on models that consider all atomic and molecular interactions and much atomic-level information can be obtained, the huge computational demand limits the models to simulations of only a few nanometers on the spatial scale and a few nanoseconds on the time scale. In order to more comprehensively study the reversible electroporation mechanism of phospholipid membrane on the nanoscale and at longer time intervals of up to 100 ns, we developed a dipalmitoylphosphatidylcholine (DPPC) phospholipid membrane model with the coarse-grained Martini force field. The model was tested by separately examining the morphology of the phospholipid membrane, the hydrophilic channel size, the distribution of the voltage potential on both sides of the membrane, and the movement of water molecules and ions during electroporation.ResultsThe results showed that the process went through several stages: (1) the formation of the pore with defects originating on the surface. (2) The maintenance of the pore. The defects expanded to large pores and the size remains unchanged for several nanoseconds. (3) Pore healing stage due to self-assembly. Phospholipid membrane shrunk and the pore size decreased until completely closed. The pores were not circular in cross-section for most of the time and the potential difference across the membrane decreased dramatically after the pores formed, with almost no restoration of membrane integrity even when the pores started to close.ConclusionsThe mechanism of the reversible electroporation process on the nanoscale level, including defects, expansion, stability, and pore closing stages on a longer time scale of up to 100 ns was demonstrated more comprehensively with the coarse-grained Martini force field, which took both the necessary molecular information and the calculation efficiency into account.

Cationic Antiseptics Facilitate Pore Formation in Model Bacterial Membranes

“…Coarse-grained (CG) approaches have the advantage of dealing with simplified molecular models, leading to larger and longer simulations with less computational efforts . The MARTINI CG force field has been proven as a very useful tool for probing interactions of chemical compounds with biological membranes (including antimicrobial peptides), exploring membrane phase transitions, pore formation, membrane fusion and disruption, and electroporation phenomena. − Here, we use CG MD simulations to study the interaction of antiseptics belonging to three chemically diverse groups of CAs (biguanidine, quaternary amine, and pyridine derivatives) with the model bacterial membrane consisting of phosphatidylethanolamine (POPE) and phosphatidylglycerol (POPG) in a 3:1 ratio.…”

A lateral electric field inhibits gel-to-fluid transition in lipid bilayers

“…[53][54][55] Second, the electric field values used in the atomistic studies are in the range of 0.05-10.2 V nm À1 . [25][26][27][28][29] The electric fields used in the experiments typically are on the order of 10 À3 V nm À1 23,56,57 but may reach a value as high as 0.08 V nm À1 . 58 The typical difference between the electric field values in simulations and experiments likely arises from the fact that the numerical studies are performed in an idealized system lacking multiple lipid species, heterogeneities and ionic concentrations.…”

“…Experimental studies have revealed electric field-induced shape transformation in giant unilamellar vesicles, [16][17][18][19][20][21] shape instabilities in membrane tubules, 22 phase separation in multicomponent membranes, 6,23 and lipid flows. 24 On the modeling front, atomistic studies [25][26][27][28][29][30] and continuum studies [31][32][33] have provided insights into the electroporation and shape transformations in vesicles.…”

Influences of Pulsed Electric Field Parameters on Cell Electroporation and Electrofusion Events: Comprehensive Understanding by Experiments and Molecular Dynamics Simulations

“…With the growth of computer technology, the molecular dynamics (MD) technique has shown tremendous promise and provides a significant insight into the process of electroporation. Accumulated evidence suggested that the rate of pore formation of phospholipid bilayers increases remarkably when exposure to a sufficiently strong electric field [19][20][21][22] . Most recently, MD simulation has also been successfully utilized to elucidate the experimental findings of the sustainable permeability of cell membranes induced by lipid peroxidation 23 .…”