Figure 3: Rate-dependent binding kinetics simulations recapitulate strain rate softening.

a, Schematic of 3D cell adhered to a substrate. The cell is decomposed into active contractile filaments and a passive Neo-Hookean matrix representing the nucleus and cytoplasm. b, Spring and dashpot representation of actin and myosin filaments in a simulated cell. c, Model incorporates reversible, force-dependent binding kinetics of myosin and actin. d, Fiber overlap length reduces when myosin heads unbind, which can result in inactive fibers. e, Simulation predictions for three cycles of stress relaxation at slow (black), medium (purple), fast (red), and trauma (yellow) strain rates. Lines represent mean of 100 simulations. Shaded regions represent 95% confidence interval. f, Violin plot of simulated normalized PK1 stress distribution after first simulated cycle of stretch. Colored horizontal lines mark the median of the distribution. Violin plots of peak and decay stress distributions after 1 cycle of simulated stretch for increased affinity (calyculin) simulations (g) and decreased affinity (Y-27632) simulations (h). i, Ratio of mean PK1 stress during fast stretch to slow stretch for untreated (black), Y-27632 (blue), and calyculin (cyan) simulations. Error bars represent 95% confidence interval.