An in vitro injury model for SH-SY5Y neuroblastoma cells: Effect of strain and strain rate

There is a great need to have in vitro cell injury model wherein a wide range of strain (e{open}) and strain rate (ε̇) can be precisely and independently applied. Such a model will enable exploration of various biomechanical loading conditions cells normally encounter during either blunt or blast impact-induced traumatic brain injuries (TBIs). In combination with a highly automated data acquisition and analysis system, this method can quickly generate a large data set of experimental results to yield identification of bio-mechanical and chemical sequelae following injury. A proper understanding of these sequelae will enable the discovery of the time window of opportunity available for pharmacological interventions. In this study we present such an injury model, a modified version of the Cultured Axonal Injury (CAI) device, and demonstrate its efficacy through viability of SH-SY5Y cells at different ranges of strain (0-140%) and strain rate (15-68s ^-1). We identified three different regimes in the stretch-induced dose-response of curves of SH-SY5Y cells, with a very sharp decline from live to dead in a narrow range of strain (30-55%). The effect of strain rate is minimal when the final strain in the cells was fixed at 50%. The model further shows that time-after-injury plays a vital role in the determination of recovery-deterioration pathways and the biological selection depends on the severity of initial injury. These data point out the initial strain level is vital to the cell fate and emphasize the need to study the various mechanisms triggered by different magnitudes of initial injuries.