Molecular dynamics simulation of cell membrane penetration by atomic force microscopy tip

In recent years, a delivery system based on atomic force microscopy (AFM) has been developed to transport nucleic acids, proteins and drugs to single adherent cell by controlling the indentation process. However, the transportation efficiency is limited by the low penetration rate of the common commercial AFM probe. The tip of commercial AFM probe is blunt and it is hard for blunt tip to insert into the soft cell membrane. In this study, dissipative particle dynamics (DPD) simulations were applied to investigate the penetration process of the AFM probe into the cell membrane subjected to different strain states. It was observed that the AFM tip moved down a shorter distance to penetrate the stretched lipid membrane compared with unstretched membrane. Moreover, the threshold value of penetrating force decreased as cell membrane extended. The short indentation time and small force can reduce the probability of cell membrane collapse, therefore it is easier for the AFM tip to penetrate the cell. We also performed the AFM indentation experiments via AFM to investigate the relationship between penetrating force and indentation speed. This work provides a potential way to improve the efficiency of cell transfection by using the AFM delivery system.