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

Stress fibersin the cytoskeleton are essential in maintaining cellularshape, and influence their adhesion and migration. Cyclic uniaxial stretching results in cellularreorientation orthogonal to the applied stretch direction via a strain avoidance reaction; the mechanistic cues in cellularmechanosensitivity to this response are currently underexplored. We show stretch induced stress fiberlengthening, their realignment and increased cortical actin in fibroblasts stretched over varied amplitudes and durations. Higher amounts of actin and alignment of stress fiberswere 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 fibergrowth and reorientation dynamics using a nonlinear, orthotropic, fiber-reinforced continuum representation of the cell. The model predicts the observed fibroblast morphology and increased cellularstiffness under uniaxial cyclic stretch. These studies are important in exploring the differences underlying mechanotransductionand cellularcontractility under stretch.