Quantifying the mechanical micro-environment during three-dimensional cell expansion on microbeads by means of individual cell-based modelling

Abstract

Controlled in vitro three-dimensional cell expansion requires culture conditions that optimise the biophysical micro-environment of the cells during proliferation. In this study, we propose an individual cell-based modelling platform for simulating the mechanics of cell expansion on microcarriers. The lattice-free, particle-based method considers cells as individual interacting particles that deform and move over time. The model quantifies how the mechanical micro-environment of individual cells changes during the time of confluency. A sensitivity analysis is performed, which shows that changes in the cell-specific properties of cell–cell adhesion and cell stiffness cause the strongest change in the mechanical micro-environment of the cells. Furthermore, the influence of the mechanical properties of cells and microbead is characterised. The mechanical micro-environment is strongly influenced by the adhesive properties and the size of the microbead. Simulations show that even in the absence of strong biological heterogeneity, a large heterogeneity in mechanical stresses can be expected purely due to geometric properties of the culture system.

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Keywords::

• individual cell-based models
• discrete element method
• three-dimensional cell expansion
• microcarriers
• mechanical micro-environment
• mechanical stress heterogeneity

Acknowledgements

This work is part of Prometheus, the Leuven Research & Development Division of Skeletal Tissue Engineering of the Katholieke Universiteit Leuven: http://www.kuleuven.be/prometheus.

Notes

^1. Porous microbeads are typically larger than non-porous microbeads, as the former can also accommodate cells inside the bead.

Additional information

Funding

Bart Smeets acknowledges the Agency for Innovation by Science and Technology in Flanders (IWT) for financial support.