Effect of Cyclic Stretch on Neuron Reorientation and Axon Outgrowth

This study investigated how cyclic uniaxial stretch influences neuronal alignment and neurite extension using PC12 cells cultured on elastomeric PDMS substrates. Using controlled stretch programs spanning amplitudes of 2–10% and frequencies of 0.05–0.25 Hz over up to 120 h, the authors quantified neurite orientation distributions and axon length from fluorescence images. Neurons exhibited clear, thresholded reorientation behavior: when stretch amplitude and frequency were sufficiently high (notably ≥5% at 0.25 Hz), cells progressively polarized toward orientations perpendicular to the stretch direction, with the fraction of perpendicularly aligned cells increasing over time. In contrast, axon elongation (mean axon length) increased with culture time but remained largely insensitive to cyclic stretch across tested conditions. To explain these results, a mechanochemical model coupling focal adhesion bond kinetics, stress fiber viscoelastic/contractile force generation, and microtubule/tubulin-driven axon growth was developed; the framework reproduced the frequency/amplitude dependence of reorientation and predicted negligible effects on axon growth for zero-mean cyclic stretch because average traction levels remain similar to static conditions.