Is cell rheology governed by nonequilibrium-to-equilibrium transition of noncovalent bonds?

A living cell deforms or flows in response to mechanical stresses. A recent report shows that dynamic mechanics of living cells depends on the timescale of mechanical loading, in contrast to the prevailing view of some authors that cell rheology is timescale-free. Yet the molecular basis that governs this timescale-dependent behavior is elusive. Using molecular dynamics simulations of protein-protein noncovalent interactions, we show that multipower laws originate from a nonequilibrium-to-equilibrium transition: when the loading rate is faster than the transition rate, the power-law exponent α₁ is weak; when the loading rate is slower than the transition rate, the exponent α₂ is strong. The model predictions are confirmed in both embryonic stem cells and differentiated cells. Embryonic stem cells are less stiff, more fluidlike, and exhibit greater α₁ than their differentiated counterparts. By introducing a near-equilibrium frequency f _eq, we show that all data collapse into two power laws separated by f/f_eq, which is unity. These findings suggest that the timescale-dependent rheology in living cells originates from the nonequilibrium-to-equilibrium transition of the dynamic response of distinct, force-driven molecular processes.