Compressional stiffening of cells and the role of the cell nucleus

What happens to a stationary cell when it is squeezed to large strains? Does the cell become increasingly rigid with compressive strain (compression stiffening) - like a soft tissue? Or does it compression soften - like an isolated fibrous network? Since the cellular cytoskeleton that gives the cell its structural support, is composed of semiflexible polymers that can buckle, one might conclude that the cell softens as it is squeezed. Experiments, however, demonstrate that cells from the ear of a mouse exhibit Hookean behavior with a crossover to superlinear behavior (compression stiffening) at large strains. We present modeling demonstrating compression stiffening in cells using rigidity transitions as a framework and show how the mechanical coupling between the cytoskeleton and the nucleus affects the stiffening. Quantitative comparisons with the experiments will be made to demonstrate the validity of the modeling and to ultimately make predictions for experiments with other cell types.