Molecular dynamics simulation of reversible electroporation with Martini force field
Abstract Background After 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 cons...
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| Format: | Article |
| Language: | English |
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BMC
2019-12-01
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| Series: | BioMedical Engineering OnLine |
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| Online Access: | https://doi.org/10.1186/s12938-019-0743-1 |
| _version_ | 1818724201875374080 |
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| author | Cheng Zhou Kefu Liu |
| author_facet | Cheng Zhou Kefu Liu |
| author_sort | Cheng Zhou |
| collection | DOAJ |
| description | Abstract Background After 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. Results The 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. Conclusions The 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. |
| first_indexed | 2024-12-17T21:22:39Z |
| format | Article |
| id | doaj.art-7a7dbb825da74b06839a607bcd1f1cc8 |
| institution | Directory Open Access Journal |
| issn | 1475-925X |
| language | English |
| last_indexed | 2024-12-17T21:22:39Z |
| publishDate | 2019-12-01 |
| publisher | BMC |
| record_format | Article |
| series | BioMedical Engineering OnLine |
| spelling | doaj.art-7a7dbb825da74b06839a607bcd1f1cc82022-12-21T21:32:08ZengBMCBioMedical Engineering OnLine1475-925X2019-12-0118111610.1186/s12938-019-0743-1Molecular dynamics simulation of reversible electroporation with Martini force fieldCheng Zhou0Kefu Liu1Department of Light Sources & Illuminating Engineering, Fudan UniversityDepartment of Light Sources & Illuminating Engineering, Fudan UniversityAbstract Background After 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. Results The 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. Conclusions The 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.https://doi.org/10.1186/s12938-019-0743-1Molecular dynamics simulationMartini force fieldReversible electroporationPhospholipid membrane |
| spellingShingle | Cheng Zhou Kefu Liu Molecular dynamics simulation of reversible electroporation with Martini force field BioMedical Engineering OnLine Molecular dynamics simulation Martini force field Reversible electroporation Phospholipid membrane |
| title | Molecular dynamics simulation of reversible electroporation with Martini force field |
| title_full | Molecular dynamics simulation of reversible electroporation with Martini force field |
| title_fullStr | Molecular dynamics simulation of reversible electroporation with Martini force field |
| title_full_unstemmed | Molecular dynamics simulation of reversible electroporation with Martini force field |
| title_short | Molecular dynamics simulation of reversible electroporation with Martini force field |
| title_sort | molecular dynamics simulation of reversible electroporation with martini force field |
| topic | Molecular dynamics simulation Martini force field Reversible electroporation Phospholipid membrane |
| url | https://doi.org/10.1186/s12938-019-0743-1 |
| work_keys_str_mv | AT chengzhou moleculardynamicssimulationofreversibleelectroporationwithmartiniforcefield AT kefuliu moleculardynamicssimulationofreversibleelectroporationwithmartiniforcefield |