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

B. Smeets, E. Tijskens, H. Ramon, H. Van. Oosterwyck, T. Odenthal
Taylor & Francis
Computer Methods in Biomechanics and Biomedical Engineering
Discrete element method, individual cell-based models, mechanical micro-environment, mechanical stress heterogeneity, microcarriers, three-dimensional cell expansion

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.

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

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