The Numerical Simulation Of Deformation Of Cell Membrane And Envelope Under Mechanical Action Of Nanoneedle

The cell penetration technology based on nanoneedle and related transfection and gene editing have becoming hot research topics in recent years.The maturity and systematization of this technology will have great significance for medicine and life sciences.However,due to the complex internal environment and structure of cells,the mechanism of mechanical penetration of cell membrane and nuclear envelope is not clear,which leads to the low mechanical penetration rate of cells and low efficiency of DNA delivery,hindering the clinical application of this technology.In the cell penetration experiment,the force transfer and the change of cell structure in the process of cell penetration could not be observed visually,which limited the progress in the study of cell mechanical penetration.Reasonable cell model and numerical simulation method can visually observe the stress distribution and deformation of each structure in the indentation process,which can promote the research on the mechanism of cell mechanical penetration.Therefore,FE models of cell membrane and nuclear envelope were established respectively in this paper to explore the stress distribution and structural deformation relationship among cell membrane,nuclear envelope,cytoskeleton and nuclear lamina under the mechanical action of nanoneedle,so as to obtain the stress changes of cell membrane and nuclear envelope during the indentation process.First,the process of indentation of cell membrane was simulated.Based on the experiments,the different nanotip and membrane conditions were simulated.Then simulated the axial and longitudinal loading of pyramid nanotip in non-orthogonal contact with the membrane.The results showed that the stress of the membrane can be divided into two stages during the indentation process.In the first stage,the stress of the membrane increases rapidly with the tip indentation.The second stage is dominated by cytoskeleton.The best cell membrane penetration occurs in the first stage.Secondly,the indentation process of nuclear envelope was simulated and divided into isolated nucleus and intact cell nucleus.For the isolated nucleus,the nanotip was loaded on the nuclear pore complex,the area near the nuclear pore and the non-pore area respectively.For the intact cell nucleus,the models have the intermediate filament component.In addition to the same three sets of simulations as isolated,a set of simulation that the tip loaded on the pore near which link to the intermediate filament was added.The results show that stress segmentation exists on the envelope.In the first stage,the envelope is tensioned,while the stress increases rapidly in the second stage.The nuclear penetration occurs in the second stage.When the nanotip is loaded on the pore near,the envelope is tensioned the fastest,and when the pore link the intermediate filament the envelope stress increases the fastest,which is most conducive to the mechanical penetration of the nuclear envelope.Finally,how to improve the penetration probability of membrane and envelope are discussed respectively.In the experiments,we can use the processed sharpened nanotip,or add drugs or proteins on the surface of the membrane/envelope to enhance their tension,and select the appropriate locating for loading to improve the penetration rate.