The cytoskeleton is one important factor in the functional and structural adaption of cells to mechanical forces. We studied the kinetics of force-induced actin and microtubules reorganization to reveal a possible communication of the two networks at uniaxial cyclic stretching of NIH 3T3 fibroblasts. As reported in the past, cells responded by a reorientation perpendicular to the stretch direction. We showed that inhibiting or enhancing actin polymerization, respectively, or blocking myosin II activity abolished the stretch-induced perpendicular cell alignment. The maximum degree in cell reorganization was independent of functional microtubules, as previously reported; however, we demonstrated that the kinetics of reorientation was microtubule-dependent. The time of cellular reorientation was reduced upon microtubule-disruption and increased upon microtubule-stabilization. We contribute this to a sterical interaction of microtubules and actin cytoskeleton where microtubules impede actin reorganization. That finding is supported by our observation of a stretch-enhanced local co-alignment of microtubules and actin stress fibers. Furthermore, we reveal that a decreased migration for myosin II-inhibited cells at non-stretched control conditions could be rescued by cyclic stretch application.

We concluded that the kinetics of the force-induced cell reorientation was influenced by an interaction of MTs and actin, whereas the final degree of orientation was MT-independent.