SpheroidSim-Preliminary evaluation of a new computational tool to predict the influence of cell cycle time and phase fraction on spheroid growth

Authored by J P Little, G J Pettet, D W Hutmacher, D Loessner

Date Published: 2018

DOI: 10.1002/btpr.2692

Sponsors: No sponsors listed

Platforms: No platforms listed

Model Documentation: Other Narrative

Model Code URLs: Model code not found

Abstract

Background There is a relative paucity of research that integrates materials science and bioengineering with computational simulations to decipher the intricate processes promoting cancer progression. Therefore, a first-generation computational model, SpheroidSim, was developed that includes a biological data set derived from a bioengineered spheroid model to obtain a quantitative description of cell kinetics. Results SpheroidSim is a 3D agent-based model simulating the growth of multicellular cancer spheroids. Cell cycle time and phases mathematically motivated the population growth. SpheroidSim simulated the growth dynamics of multiple spheroids by individually defining a collection of specific phenotypic traits and characteristics for each cell. Experimental data derived from a hydrogel-based spheroid model were fit to the predictions providing insight into the influence of cell cycle time (CCT) and cell phase fraction (CPF) on the cell population. A comparison of the number of active cells predicted for each analysis showed that the value and method used to define CCT had a greater effect on the predicted cell population than CPF. The model predictions were similar to the experimental results for the number of cells, with the predicted total number of cells varying by 8\% and 12\%, respectively, compared to the experimental data. Conclusions SpheroidSim is a first step in developing a biologically based predictive tool capable of revealing fundamental elements in cancer cell physiology. This computational model may be applied to study the effect of the microenvironment on spheroid growth and other cancer cell types that demonstrate a similar multicellular clustering behavior as the population develops. (c) 2018 American Institute of Chemical Engineers Biotechnol.

Tags

Agent-based model Simulation mathematical modeling Multiscale Resistance Ovarian-cancer Bioengineering Cancer spheroids Cell growth Cancer spheroids