Finite Element Simulation Of Cell Damage Based On Gene Gun

Nowadays,cancer is one of the main causes of human deaths.In an effort to search for effective treatment of cancers,gene therapy technology based on gene gun has emerged.The basic principle of the gene gun technology is to shoot tungsten or gold particles coated with DNA into the target cells in a physical way with an accelerator device to achieve the expression of foreign genes.However,the use of the gene gun also faces obstacles.For example,it is difficult to inject the microprojectile containing DNA into the target cell at an appropriate speed without severely damaging or destroying the cell,which affects the gene expression rate and the experimental success rate.In order to solve this problem,this paper uses a combination of biological experiments and numerical simulations to establish a cell damage model,which will provide a new modelling tool to analyze gene gun experiments in advance for improvement.Based on the previous studies,this paper combines an atomic force microscopy(AFM)membrane rupture experiment,a cell theory model and a cell finite element model to simulate the process of cell membrane being perforated by AFM probe from the mechanical point of view,and to establish a quasi-static Hela cell model.The damage model is then used to obtain the necessaryconditions for membrane damages,and on this basis,the possibility of dynamic damage simulation of the gene gun is discussed.Main tasks carried out are listed as follows:1)Hela cells were subjected to membrane rupture experiments using AFM.First,cells were scanned to obtain the surface topography parameters.Secondly,the AFM probe was used to ‘press then puncture' the cells at a height of about3.5 ?m to obtain the probe force-displacement curve,from which the material parameters of the cell membrane can be obtained.2)The basic hypothesis of the cell model was proposed.The common constitutive model of cell membrane and cytoplasm was analyzed,and a cell mechanics model with two different material properties has been established for the cell.The results show that it is more accurate and reasonable to establish an elastoplastic model for the cell membrane and establish a viscoelastic model for the cytoplasm.3)The AFM membrane rupture experiment was simulated using an FEA package ABAQUS.By fitting the simulation outcomes with the experimental results,plastic parameters were deducted which cannot be directly measured in the experiment.On this basis,an initial trial was established for the dynamic model of a microprojectile impact to the cell.The simulation results show that there are different effects on cell deformation under different initial velocity conditions.Only when the appropriate speed is set,the microprojectile can breakthrough the cell membrane then stay inside the cell,resulting to the potential expression of the genes.Cell experiments and finite element simulations were used as research methods to establish a quasi-static cell damage model in this research.Based on this,a preliminary attempt was made to simulate the microprojectile penetration into a cell,which makes it possible to study high-speed impact to cells by using a gene gun.The research also provides a potential new method for studying cell mechanics in future studies.