Biomechanical and Nutrient Controls in the Growth of Mammalian Cell Populations

Abstract

Growth kinetics and morphologies of growing mammalian cell populations are part of the growth dynamics of tumors. A biophysical agent-based simulation model describes a biological cell by a homogeneous elastic adhesive object able to migrate, grow and divide, and die. A comparison of simulation results with experimental data shows that the growth kinetics of growing multicellular spheroids (MCS) over a wide range of nutrient concentrations is explained by a bio-mechanical form of contact inhibition between cells. This inhibition mechanism explains the growth kinetics of the tumor diameter and the cell population size, the size of the necrotic core, the median cell volume, which decreases when the tumor diameter increases, and the spatial distribution of cell volumes in the tumor. The same model is used to predict how cell populations survive in low nutrient concentrations. Spatial patterns are different for changes of the cell phenotype by regulation or mutation. The cells appearing in the simulations decrease cell-cell adhesion, display chemotaxis movement, increase micro-motility and decrease cell cycle time. Each of these have been observed in invasive cancers.

Keywords:

• agent-based simulation
• biochemical constraints
• growth dynamics
• johnson-kendall-roberts theory
• nutrient control
• tumor

ACKNOWLEDGMENT

Stefan Hoehme acknowledges support by the EU-grant PASSPORT and the BMBF-grant HepatoSys. Dirk Drasdos work is supported by the EU-grants CancerSys and PASSPORT, and the BMBF-grants LungSys under 0315415F and HepatoSys under 313074D.