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.