A stochastic mathematical model of 4D tumour spheroids with real-time fluorescent cell cycle labelling.

In vitro tumour spheroids have been used to study avascular tumour growth and drug design for over 50 years. Tumour spheroids exhibit heterogeneity within the growing population that is thought to be related to spatial and temporal differences in nutrient availability. The recent development of real-time fluorescent cell cycle imaging allows us to identify the position and cell cycle status of individual cells within the growing spheroid, giving rise to the notion of a four-dimensional (4D) tumour spheroid. We develop the first stochastic individual-based model (IBM) of a 4D tumour spheroid and show that IBM simulation data compares well with experimental data using a primary human melanoma cell line. The IBM provides quantitative information about nutrient availability within the spheroid, which is important because it is difficult to measure these data experimentally.

Finite transition times for multispecies diffusion in heterogeneous media coupled via first-order reaction networks.

Calculating how long a coupled multispecies reactive-diffusive transport process in a heterogeneous medium takes to effectively reach steady state is important in many applications. In this paper, we show how the time required for such processes to transition to within a small specified tolerance of steady state can be calculated accurately without having to solve the governing time-dependent model equations. Our approach is valid for general first-order reaction networks and an arbitrary number of species. Three numerical examples are presented to confirm the analysis and investigate the efficacy of the approach. A key finding is that for sequential reactions our approach works better provided the two smallest reaction rates are well separated.