A Computational Model of Mechanical Stretching of Cultured Cells on a Flexible Membrane

In this study, we developed a computational model of a cell being stretched on a flexible membrane, a configuration that matches many in vitro experimental systems studying the effects of mechanical stretch on cultured cells. Using this model, we explored the complex patterns of stresses and strains present in the cell during dynamic stretching. We linked these intracellular stresses to a simple model of chromatin deformation to provide a rough estimate of chromatin reconfiguration resulting from nuclear strain. Together, this multiscale model of cell stretching offers a first-order approximation of cellular strain responses to dynamic substrate deformation. Our simulations identified an optimal range of applied strain that induces chromatin distention without causing cellular damage. This computationally determined optimal strain range aligns with recent experimental findings from our laboratory, where the same strain levels were shown to maximize nuclear localization of Yap/Taz and reduce senescence in mesenchymal stem cells (MSCs). These results provide a computational framework for understanding cellular responses to mechanical stimuli, potentially optimizing experimental designs and advancing the understanding of mechanobiology in stem cell research and tissue engineering applications.