title: 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.
authors.affiliation: a KU Leuven - MeBioS , Kasteelpark Arenberg 30, 3001 , Heverlee , Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: Smeets
authors.forename: Tim
authors.initials: T
authors.lastname: Odenthal
authors.forename: Engelbert
authors.initials: E
authors.lastname: Tijskens
authors.forename: Herman
authors.initials: H
authors.lastname: Ramon
authors.forename: Hans
authors.initials: H
authors.lastname: Van Oosterwyck
mesh_terms: D002448:Cell Adhesion; D018929:Cell Culture Techniques; D002453:Cell Cycle; D049109:Cell Proliferation; D008863:Microspheres; D008954:Models, Biological; D013314:Stress, Mechanical