Control of stress propagation in the cytoplasm by prestress and loading frequency

One fundamental question in cell biology is how mechanical stresses are distributed inside the cytoplasm. Recently we have developed a synchronous detection approach to map cytoplasmic displacements and stresses using yellow fluorescent protein tagged mitochondria as fiducial markers of the cytoskeleton (CSK) in response to a localized load applied via an RGD-coated magnetic bead (7). We have shown that stresses are propagated to remote sites in the cytoplasm, a finding that contradicts continuum model predictions. Here we show that long distance force propagation in the cytoplasm was abolished when the contractile prestress in the CSK was lowered by relaxing agents and enhanced when the prestress was increased by contractile agonists. Surprisingly, when the loading frequency was varied from 0.03 Hz to 30 Hz, the total area of induced displacements (an index of the extent of stress propagation) first increased with loading frequency and then decreased with loading frequency. These results demonstrate that the long distance force propagation in living adherent cells might be controlled by the level of contractile prestress in the CSK and by the loading frequency.