Understanding how a human cell reacts to external physical stimuli is essential to understanding why vibration can elicit localized pain reduction. Stimulation of epithelial cells with external vibration forces has been shown to change cell shape, particularly in regards to structures involved in non-muscle cell motility. We hypothesized that epithelial cells respond to vibration transduction by altering proteins involved in remodeling cytoskeleton. Epithelial cells were exposed to vibration and assessed by microscopy, cytoskeletal staining, immunoblotting and quantitative RT-PCR. Here, we report that epithelial cell lines exposed to 15 minutes of vibration retract filopodia and concentrate actin at the periphery of the cell. In particular, we show an increased expression of the calcium-dependent, cysteine protease, calpain. The discovery that cell transitions are induced by limited exposure to natural forces, such as vibration, provides a foundation to explain how vibrational treatment helps migraine patients.