Cyclic Stretch-Induced Mechanical Stress Applied at 1 Hz Frequency Can Alter the Metastatic Potential Properties of SAOS-2 Osteosarcoma Cells

This study examined how mild cyclic uniaxial stretch modulates morphology and metastatic-associated behaviors in SAOS-2 osteosarcoma cells. Cells cultured on deformable silicone plates were subjected to 0.5% elongation at 1 Hz for 24 h (intermittent loading), followed by quantitative morphometry (AFM and confocal microscopy), viability/differentiation readouts, and functional motility assays. Mechanical stimulation increased nuclear surface area (~1.3×) while maintaining nuclear eccentricity, doubled whole-cell spread area, and further elongated cell shape, alongside a reduced nuclear-to-cytoplasmic ratio (~22%) and increased peripheral membrane roughness (~40%). These morphological changes were not accompanied by altered osteoblastic differentiation markers (RUNX2,COL1A1,ALPL) or ALP activity. Functionally, pre-stretched cells displayed decreased adhesion and markedly increased migration and transmigration. Secreted pro-MMP-2 gelatinolytic activity increased, but pharmacologic MMP inhibition did not reverse stretch-induced motility, whereas mechanosensitive stretch-activated ion-channel blockade (GsMTx4) significantly attenuated the increased migration/transmigration, implicating ion-channel-mediated mechanosensing in the pro-migratory response.