| Popis: |
Co-culture tumour spheroid experiments are routinely performed to investigate cancer progression and test anti-cancer therapies. Therefore, methods to characterise and interpret coculture spheroid growth are of great interest. However, co-culture spheroid growth is complex. Multiple biological processes occur on overlapping timescales and different cell types within the spheroid may have different characteristics, for example proliferation rate or response to nutrient availability. There is no standard, widely-accepted mathematical model of such complex spatio-temporal growth processes. Typical approaches to analyse these experiments focus on the late-time temporal evolution of spheroid size and overlook early-time spheroid formation, spheroid structure and geometry. Here we make theoretical and practical contributions. We develop a general framework, based on mathematical and statistical modelling, to analyse a series of co-culture experiments. Using a range of different mathematical models we provide new biological insights about spheroid formation, growth, and structure. In addition, we extend a general class of compartment-based monoculture spheroid mathematical models to describe multiple populations and provide mechanistic biological insight. The framework is well-suited to analyse spheroids grown with multiple different cell types and the new class of mathematical models provide opportunities for further mathematical and biological insights. |
