External electric field effect on the translocation of R-derivatives peptides across a symmetric lipid bilayer using umbrella sampling


Translating cargoes like nanoparticles (NP) and macromolecules like DNA and RNA across the model membrane through different cell-penetrating peptides (CPPs) has been the point of research for the last few years. Electroporation is a technique to transfer foreign molecules like proteins, drugs, antibodies, and highly charged molecules such as DNA into the cell membrane. However, how the external electric field helps increase the membrane permeability hasn’t been elucidated yet. Therefore, in this MD study, the presence and the absence of a constant electric field effect were studied during the interaction of oligoarginine peptides (R4, R8) with the symmetric lipid bilayer having the following lipid composition: DOPC/DOPG(4:1). The results showed, initially, there was not a significant free energy barrier difference for tetra-arginine with and without electric field, but after 100ns of simulation it starts showing a noticeable difference with a higher value for without electric field than with electric field. However, initially, with and without an external electric field, the octa-arginine case showed almost the same barrier. After 100ns, there was a minor difference in the free energy barrier with a higher of a few kJ/mol of magnitude in the presence of an electric field than in an electric field absence. The outcome seems consistent with the fact that the applied electric field must have a threshold value to generate the membrane defect and transmembrane pore to lower the free energy cost. This study explains the external electric field effect on the translocation of R-derivative peptides through the symmetric membrane.

2023 KPS Spring Meeting (04/19-04/21, Daejeon)