ARUP; ISBN: 978-0-9562121-5-3 - CMBBE 2012 - Cardiff University

Average stress [Pa]
14
12
10
8
6
4
2
0
-2
-4
2.5e-6 5e-6 10e-6 20e-6 40e-6
Cell-Bead adhesion [J/m 2 ]
(a)
Average stress [Pa]
8
6
4
2
0
-2
-4
250 500 1000 2000 4000
Substrate Stiffness [Pa]
Figure 4: (a): stress levels in simulated microcarrier cell expansion for different cell-substrate adhesion
values (b): stress levels for different microcarrier stiffness values
5 CONCLUSION AND OUTLOOK
The developed IBM provides an interesting theoretical model system for cell expansion on microcarriers.
We show that for a system of cells which have mechanical properties comparable
to progenitor cells, a large range of mechanical stressses can be expected, purely resulting from
effects of geometry and mechanical process design parameters. This gives a proof of principle
that theoretically, a large biological heterogeneity is not required to result in a heterogenous mechanical
microenvironment. Given that cell behaviour and cell fate are strongly influenced by the
mechanical microenvironment, it is not unreasonable to assume that from a population of cells
which are biologically identical, a large phenotypical heterogeneity might occur purely due to
spatial and mechanical phenomena.
At this stage, the model provides mostly theoretical insights, which are not validated for direct
practical use in cell culture. We modeled the mechanical properties of cells as homogenous and
constant. However, the visco-elastic properties of cells are often very heterogenous and can change
in time due to restructuring of the cytoskeleton. Therefore it is essential that the mechanical properties
of the modeled cells are measured as accurately as possible at all timepoints in the cell
expansion. As more and more computational power becomes available, the modeled aggregate
size can become bigger and the complexity of cell shape and mechanics can be increased. Cell
shape could be modeled more accurately by making use of subcellular elements that interact with
each other through visco-elastic potentials [12].
Finally, this study only considered the influence of a few selected process design parameters.
However, in reality these parameters might actually influence eachother. Hence, a complete study
of the full parameter space will be done to reveal correlations between different model parameters.
ACKNOWLEDGEMENT
Agency for Innovation by Science and Technology in Flanders (IWT)
(b)