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

## TL;DR

This paper introduces a computational model to study how mechanical stretching affects cells on flexible membranes, linking strain to chromatin deformation and identifying optimal strain ranges for cell health.

## Contribution

The novel contribution is a multiscale computational model that connects mechanical strain to chromatin deformation and identifies an optimal strain range for cell function.

## Key findings

- Simulations identified an optimal strain range that distends chromatin without causing cellular damage.
- The optimal strain levels align with experimental results showing increased nuclear localization of Yap/Taz and reduced senescence in MSCs.
- The model provides a framework for understanding cellular responses to mechanical stimuli in tissue engineering.

## Abstract

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.