Computational Mechanobiology in Cartilage and Bone Tissue Engineering: From Cell Phenotype to Tissue Structure - Computational Modeling in Tissue Engineering - page 336

Fig. 1 Steady-state actin stress-fibre distribution in a fibroblast on a micropost array (left) and
corresponding simulation results based on McGarry et al. [ 75 ](right). Contours illustrate the
degree of stress fibre formation, vectors correspond to the dominant stress fibre direction. Images
courtesy of Dr. Patrick McGarry, Mechanical and Biomedical Engineering, NUI Galway, Ireland
conjunction with a displacement produces that mechanical work. This work can
now be minimised by the cell in different ways: If the substrate stiffness increases,
the cell has to strain the ECM less to create a given level of force which corre-
sponds to less work being invested. A prestrain of the substrate is shown to lower
the work as well and hence corresponds to an effective stiffening. In terms of the
wider concepts of modelling the authors make a statement that holds for
phenomenological models in general and thus fits the general context of this
chapter: ''It is important to note that conceptually the principle suggested here
does not imply that the cell actually minimizes the work W invested into its soft
environment. Instead we suggest here that calculating the quantity W for different
situations of interest is an appropriate measure for the kind of information a cell
can extract from its elastic environment through active mechanosensing. The real
justification of our model will be its success in explaining a large body of
experimental data'' [ 6 ]. Nevertheless, the considerations imply a mechanism by
which higher matrix stiffness leads to an increased efficiency in the up-regulation
of cell-matrix contact points. Based on the work optimisation principle, the model
predicted cell alignment parallel and perpendicular to free and clamped edges,
respectively, cell alignment with applied tensile strain and coalignment of cells
into strings. Cells were further predicted to have a tendency of moving away from
free surfaces and the model can potentially explain certain aspects of cell
behaviour that cannot be established based on contact guidance models [ 3 ]. Cell
alignment in response to ECM alignment, i.e. contact guidance, is relevant for
tissue engineering applications and soft scaffold contraction. To allow a theoretical