Mechanical cues from the environment influence cell behavior. Mechanisms of cellular mechanosensation are unclear, partially due to a lack of methods that can reveal dynamic processes. Here, we present a new concept for a low-cost, magnetically-driven device that enables high-magnification imaging of cells during stretch. Using this device, we observed that nuclei of mouse embryonic skin fibroblasts underwent rapid but divergent responses to strain magnitude, showing area increase and chromatin

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... decompaction during 5% strain, but area decrease and chromatin condensation during 20% strain. Only responses to low strain were dependent on calcium, while actin inhibition abrogated any nuclear response and increased stretch-induced DNA damage. Stretch-activation revealed a shift in actin filaments away from (5% strain) or towards (20% strain) the nuclear periphery. Our findings suggest that different pathways control strain level-dependent cell behavior and that mechanical confinement of nuclei through actin may be a protective mechanism during high strain loads.