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

  • Smeets B
  • Odenthal T
  • Tijskens E
 et al. 
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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.

Author-supplied keywords

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

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Authors

  • Bart Smeets

  • Tim Odenthal

  • Engelbert Tijskens

  • Herman Ramon

  • Hans van Oosterwyck

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