Biomedical Modeling Study Of The Influence Of Mechanical Environment On Metastatic Tumor’s Growth And Invasion

The growth,invasion and treatment of metastases are closely related to the current mechanical microenvironment.However,there is currently no effective means to obtain the dynamic changes of the intratumoral mechanical microenvironment.Through the in vivo experiments,the global stress distribution in the tumor area cannot be directly obtained.There are still many difficulties in describing the dynamic changes in the microenvironment of tumor mechanics by means of numerical simulation.The discrete element method is widely used to study the motion and macroscopic mechanical properties of a large number of micro-scale particles.Therefore,based on the idea of discrete element modeling,the dynamic process of metastatic tumor growth coupled with the mechanical environment is studied through mathematical modeling,numerical simulation and experimental verification.Based on the basic idea of the discrete element,the model uses three types of discrete circular cells to represent the three basic substances inside the tumor: tumor cells,host cells,and cell mesenchyme,and gives each unit mechanical parameters,mainly including: stiffness,viscosity,Surface friction coefficient,shear stiffness,etc.The interaction between cells and cells and between cell and cell matrix is represented by the elastic-viscous connection.Hooke’s law is used to define the constitutive relationship between the binding force and the unit displacement.The movement of the basic unit satisfies Newton’s second law.The model introduces tumor cell proliferation and proliferation in the description of tumor physiology and considers two basic cell phenotypes: active tumor cells and resting tumor cells.The iterative solution process is to solve the force of each basic unit to obtain the unit velocity and acceleration,and iteratively updates the position information of each tumor cell to obtain new unit force information until the boundary of the calculation area and the peripheral tissues reach equilibrium.Using the established discrete model of metastatic tumor growth,the early morphological and mechanical microenvironment of metastatic tumors can be studied with the changes of tumor growth.The former includes: morphological changes of tumor growth,number and density of tumor cells,and tumor regional scale;Specifically,it includes: the compression force of the tumor area to the outside tissues,the stress field of the tumor area,and the like.The simulation results are qualitatively consistent with the in vitro experimental results.The effect of the mechanical microenvironment where the metastasis is located on the growth and invasion of metastases was also studied by the model.Further,using the established metastasis growth model and the method of controlling variables,the effects of various mechanical parameters of tumor cells and host cells on the growth,invasion and mechanical environment of metastases were discussed.The results show that the normal stiffness of the cell surface has the most significant effect on the stress microenvironment and tumor morphology of the tumor calculation area.Through model calculation and discussion of model parameters,it can provide a theoretical basis for the clinical treatment of metastases by changing the mechanical microenvironment.