Prediction of changes in cell-substrate contact under cyclic substrate deformation using cohesive zone modelling

The in vitro reorientation of isolated cells under conditions of cyclic substrate stretching is widely reported in the literature; see, for example, Wang et al. (1995), Takemasa et al. (1998) and Neidlinger-Wilke et al. (2001). Such behavior is observed for a variety of cell phenotypes including fibroblasts, human melanocytes and endothelial cells.Wang et al. (2001) report that under uniaxial substrate stretching, where substrate contraction is prohibited, cells were found to align at 90? to the direction of stretching. In cases where lateral substrate contraction was permitted cells were found to align at 65? to the direction of stretching. Both alignment directions correspond to the direction of minimum substrate strain. However, it is not clear from such in vitro studies why such cell reorientation occurs. In the current study computational models are developed in order to elucidate the mechanisms underlying such behavior. Two cohesive zone models are considered for modeling of cell-substrate adhesion (Beltz and Rice (1991), Xu and Needleman (1993)). Cells are modeled as a viscoelastic continuum. Such an approach to cell modeling has been shown by Leipzig and Athanasiou (2004) to provide better predictions for initial creep response than the alternative bi-phasic modeling approach. Viscoelastic properties are fitted to the experimental measurements of Sato et al. (1990) for porcine endothelial cells.