Molecular Dynamics Study Of Cell Membrane Electroporation Induced By Picosecond Electric Pulses

In recent years,a wide range of applications of membrane electroporation have been found in biological and medical fields.Especially,the electroporation induced by picosecond electric pulses has shown great potential in the field of cancer treatment.However,the physical mechanism of membrane electroporation induced by picosecond electric pulses is still unclear.To give the physical mechanism of the electroporation induced by picosecond pulses,and better apply this tool to the biomedical field,in this paper the membrane electroporation induced by picosecond electric pulses are investagated by means of molecular dynamic simulations.The main work and innovation points are as follows:1.The molecular dynamic model of cell membrane electroporation induced by picosecond electric pulses is established,and the physical mechanism of the electroporation induced by unipolar picosecond pulses is found.The electroporation process with the applied monopolar picosecond pulses are calculated,and it is compared with the electroporation induced by the conventional constant electric field.Then it is found that the average pore formation time increases when the pulse repetition frequency increases.The dipole moments of water molecules have been studied,and it is shown that the decrease in water oriented polarization degree leads to an increase in the pore formation time.At the same time,the result has displayed that an abnormal variation region of 0.4 THz?0.5 THz that shows decline exists on the correlation curve of the average pore formation time and the pulse frequency.The abnormal variation region appearance is related to the drastic change of average water hydrogen bond number that is resulted from the resonance of water hydrogen bond network and the applied electric field.2.The condition required for the symmetrical bipolar picosecond pulses to induce electroporation is given,and the influence of symmetrical bipolar picosecond pulse parameter variations on electroporation is studied.It is shown that,for a certain repetition frequency,the pore can form only when the pulse amplitude is greater than the threshold value,and for a certain pulse amplitude,the pore can form only when the repetition frequency is less than the threshold value.Additionally,discrete nanoscale pores can form with the applied bipolar picosecond pulses at terahertz(THz)repetition frequency.When the pulse amplitude increases or the frequency decreases,the number of water bridges will increase.3.The mechanism of effect of bipolar asymmetric pulse waveform variation on the electroporation has been studied.It is found that with the increase in the intensity of the reverse electric pulse,the pore formation time increases first and then decreases.Then the reason for this phenomenon is given through the study of the water molecules of the system.Furthermore,the impact of the intensity and repetition frequency of the bipolar asymmetric pulse on the perforation is calculated.The results show that the pore formation time decreases when the pulse intensity increases,and the pore formation time becomes longer when the repetition frequency increases.4.The physical mechanisms of electroporation bipolar cancellation are found through the study of the electric field force,the water dipole moment and the electric field gradient of the system.It shows that the direction of bipolar electric force on the interfacial water molecule reverses as the bipolar pulse reverse,while the electric force on interfacial water molecule of the cathode side keeps in the same direction with applied monopolar pulse.Besides,the reason for the reversal of bipolar cancellation is also given.At last,the effect of pulse width on the cross point intensity of two different pulses is studied.The cross point intensity of two different pulses increases,as the pulse width decreases.This discovery can help us understand the experimental results of bipolar cancellation and its reversal.5.The mechanism of the influence of KcsA channel presence on cell membrane electroporation induced by picosecond electric pulses is proposed.First,it is discovered that the average pore formation time of the KcsA system is longer than the bare system with the applied picosecond pulses.Then the influence of the model size variation with the applied picosecond pulse is studied.When the system size decreases,the average pore formation time of small KcsA membrane protein system is shorter than the bare system with the applied picosecond pulses.Finally,the reason for the influence of membrane protein existence on electroporation with the applied picosecond pulses is given through the analysis of KcsA protein rmsf value,protein dipole moment and interfacial water dipole moment.This work has provided some new ideas for the application of cell membrane electroporation in biomedicine.