Micro-environmentally restricted cell growth dynamics - modeling considerations

Various modeling approaches have been applied to describe the rearrangement of immobilized cell clusters within the extracellular matrix. The cell rearrangement has been related with the micro-environmental restrictions to cell growth. Herein, an attempt is made to discuss and connect various modeling approaches on various time scales which have been proposed in the literature in order to shed further light to this complex phenomenon which induces micro-environmental restrictions to cell growth. The rearrangement is driven by internal stress generated within the cluster. The internal stress represents a consequence of the matrix rheological response to cell expansion. The rearrangement includes the interplay between the processes of: (1) single and collective cell migrations, (2) cell deformation and orientation, (3) decrease of cell-to-cell separation distances and (4) cell growth. It has been considered on two time scales: a short time scale (i.e. the rearrangement time) and a long time scale (i.e. the growing time). The results indicate that short and long times cell rearrangement induces energy dissipation. The dissipation provokes biological responses of cells which cause the resistance effects to cell growth. Deeper insight in the anomalous nature of the energy dissipation would be useful for understanding the biological mechanisms which causes the resistance effects to cell growth.