Stress fiber growth and remodeling determines cellular morphomechanics under uniaxial cyclic stretch

Stress fibers in the cytoskeleton are essential in maintaining cellular shape, and influence their adhesion and migration. Cyclic uniaxial stretching results in cellular reorientation orthogonal to the applied stretch direction via a strain avoidance reaction; the mechanistic cues in cellular mechanosensitivity to this response are currently underexplored. We show stretch induced stress fiber lengthening, their realignment and increased cortical actin in fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and alignment of stress fibers were accompanied with an increase in the effective elastic modulus of cells. Microtubules did not contribute to the measured stiffness or reorientation response but were essential to the nuclear reorientation. We modeled stress fiber growth and reorientation dynamics using a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the observed fibroblast morphology and increased cellular stiffness under uniaxial cyclic stretch. These studies are important in exploring the differences underlying mechanotransduction and cellular contractility under stretch.