Effect of Brief Electrical Stimulation on Cell Biomechanics in Hereditary Sensory Neuropathy

Abstract SH‐SY5Y neuroblastoma cells are widely used to model neurodegenerative disorders like Alzheimer's, Parkinson's, Huntington's, and Hereditary Sensory Neuropathy type 1A (HSN‐1A), a peripheral nerve condition causing axon degeneration and sensory loss. A cell model of HSN‐1A is developed by overexpressing wild‐type and mutant SPTLC1 genes (C133W, C133Y, V144D). Cells are cultured on plastic and gold substrates, with brief electrical stimulation applied to the gold‐grown cells. Atomic force microscopy (AFM) is used to measure Young's modulus, indentation, and energy dissipation. Finite Element Method and non‐linear modeling validate the results. In the absence of stimulation, mutant cells show lower stiffness compared to non‐transfected cells, indicating a direct biomechanical impact of the mutations. Brief electrical stimulation significantly increases the stiffness of mutant cells, particularly in C133W (99%), C133Y (100%), and V144D (111%) variants, despite the mutations. Energy dissipation of stimulated V144D cells decreases to levels comparable to untreated non‐transfected cells. The simulations support the AFM measurements, demonstrating that brief electrical stimulation can partially reverse the biomechanical effects of gene mutations.