Biophysical insights into the impact of lateral electric field stimulation to cellular microenvironment: Implications for bioelectronic medicine applications

In the last few decades, electrical stimulation devices have been clinically used for a wide spectrum of applications, ranging from deep brain stimulation to drug and gene delivery. Despite such clinical relevance, the impact of electrical stimulation on the cellular biophysical processes has not been explored significantly. We report here the analytical results to develop quantitative biophysical insights into the influence of lateral electric field stimulation on bioelectric stresses in the intercellular/extracellular region and the membrane tension. In developing quantitative insights, we solved Laplace equation with appropriate boundary conditions in an azimuthally asymmetric system with a single cell. The magnitude of the stresses increases with the electric field strength in a parabolic manner. In case of cell without surface charges, the intracellular stress field is predicted to have both compressive and tensile regions with a maximum of 2 μPa, while a maximum tensile stress of 20 μPa in extracellular region could be predicted, at field strength of 300 V/m. While considering surface charges, the magnitude of extracellular normal and shear stresses at the cell membrane is an order of magnitude higher when compared to without surface charges. Based on the variation of shear stress tensors at cell membrane, the critical field strength for membrane rupture was found to be 5.3 kV/mm and 20 kV/mm for a cell without and with surface charges respectively. The impact of the bioelectric stresses on the mechanotransduction induced cytoskeletal reorganization and stress driven cellular signalling modulation were substantiated using quantitative results from the study.