Activity-dependent glassy cell mechanics I : Mechanical properties measured with active microrheology

The active microrheology was conducted in living cells by applying optical-trapping force to vigorously-fluctuating tracer beads with the feedback-tracking technology. Complex shear viscoelastic modulus G(ω) = G′ (ω) − iG″(ω) was measured in HeLa cells in an epithelial-like confluent monolayer. We found that G(ω) ∝ (−iω)0.5 in large range of frequencies (0.1 Hz < ω 2π <10 kHz). Actin disruption and cell-cycle progression from G1 to S, G2 phases only limitedly altered G(ω) in living cells. On the other hand, G(ω) was dependent on cell metabolism; the ATP-depleted cells increased elastic modulus G′ (ω) at low frequencies by giving rise to a constant plateau as G(ω) = G0 + A(−iω) 0.5. Both the plateau and the additional frequency dependency proportional to (−iω)0.5 of ATP-depleted cells are consistent to the typical rheological response of colloidal jamming. On the other hand, the plateau G0 disappeared in the ordinary metabolically active cells, implying that the living cells fluidize their internal states towards critical jamming point. Statement of Significance Intracellular mechanical properties were measured using the optical-trap-based microrheology. Despite the common expectations, shear viscoelasticities were hardly concerned with reorganization of cytoskeletal structures during cell-cycle progressions, nor with the artificial disruption of actin cytoskeletons induced with chemical inhibitors. Rather, the mechanics of cell interiors were governed by the glassy cytoplasm. Rubber-like elasticities in solidified ATP-depleted cells disappeared in living cells with ordinary metabolic activities, indicating the activity-dependent fluidization. Instead of the complete fluidic response, however, we observed the characteristic power-law viscoelasticities G(ω) ∝ (iω)0.5 in the whole range of frequencies observed. Based on the recent understanding of jamming rheology, we discuss that cells fluidize their internal state towards the critical jamming transition.