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

Peter J. Little, G. J. Pettet, D. W. Hutmacher, D. Loessner

Research output: Contribution to journalArticleResearchpeer-review

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.

Original languageEnglish
Pages (from-to)1335-1343
Number of pages9
JournalBiotechnology Progress
Volume34
Issue number6
DOIs
Publication statusPublished - Nov 2018
Externally publishedYes

Keywords

  • agent-based model
  • bioengineering
  • cancer spheroids
  • cell growth
  • Mathematical modeling

Cite this