Design, implementation, and validation of a piezoelectric device to study the effects of dynamic mechanical stimulation on cell proliferation, migration and morphology

Cell functions and behavior are regulated not only by soluble (biochemical) signals but also by biophysical and mechanical cues within the cells' microenvironment. Thanks to the dynamical and complex cell machinery, cells are genuine and effective mechanotransducers translating mechanical stimuli into biochemical signals, which eventually alter multiple aspects of their own homeostasis. Given the dominant and classic biochemical-based views to explain biological processes, it could be challenging to elucidate the key role that mechanical parameters such as vibration, frequency, and force play in biology. Gaining a better understanding of how mechanical stimuli (and their mechanical parameters associated) affect biological outcomes relies partially on the availability of experimental tools that may allow researchers to alter mechanically the cell's microenvironment and observe cell responses. Here, we introduce a new device to study in vitro responses of cells to dynamic mechanical stimulation using a piezoelectric membrane. Using this device, we can flexibly change the parameters of the dynamic mechanical stimulation (frequency, amplitude, and duration of the stimuli), which increases the possibility to study the cell behavior under different mechanical excitations. We report on the design and implementation of such device and the characterization of its dynamic mechanical properties. By using this device, we have performed a preliminary study on the effect of dynamic mechanical stimulation in a cell monolayer of an epidermal cell line (HaCaT) studying the effects of 1 Hz and 80 Hz excitation frequencies (in the dynamic stimuli) on HaCaT cell migration, proliferation, and morphology. Our preliminary results indicate that the response of HaCaT is dependent on the frequency of stimulation. The device is economic, easily replicated in other laboratories and can support research for a better understanding of mechanisms mediating cellular mechanotransduction.The work by D.M. has been performed in the frame of an FPU Program, FPU015/06208, granted by the Spanish Ministry of Education, Culture and Sports. This work has been funded by the Comunidad de Madrid under de grant BIOPIELTEC-CM (P2018/BAA-4480) and the Ministerio de Ciencia e Innovación under de grant Paraqua (TEC2017-86271-R). The authors acknowledge the support by Francisco J. Rodríguez in the physical analysis of the applied forces