A multiscale model for heterogeneous tumor spheroid in vitro.

In this paper, a novel multiscale method is proposed for the study of heterogeneous tumor spheroid growth in vitro. The entire tumor spheroid is described by an ellipsoid-based model while nutrient and other environmental factors are treated as continua. The ellipsoid-based discrete component is capable of incorporating mechanical effects and deformability, while keeping a minimum set of free variables to describe complex shape variations. Moreover, our purely cell-based description of tumor avoids the complex mutual conversion between a cell-based model and continuum model within a tumor, such as force and mass transformation. This advantage makes it highly suitable for the study of tumor spheroids in vitro whose size are normally less than 800 μm in diameter. In addition, our numerical scheme provides two computational options depending on tumor size. For a small or medium tumor spheroid, a three-dimensional (3D) numerical model can be directly applied. For a large spheroid, we suggest the use of a 3D-adapted 2D cross section configuration, which has not yet been explored in the literature, as an alternative for the theoretical investigation to bridge the gap between the 2D and 3D models. Our model and its implementations have been validated and applied to various studies given in the paper. The simulation results fit corresponding in vitro experimental observations very well.