Neuronal response to high rate shear deformation depends on heterogeneity of the local strain field

Many cellular models of traumatic brain injury (TBI) deform cells in a planar (2-D) configuration, a contrast from the three-dimensional (3-D) architecture of the brain, resulting in strain fields that may fail to represent the complex deformation patterns seen in vivo. Cells cultured in 3-D may more accurately represent in vivo cellular behavior than planar models due to differences in cytostructure, cell-cell/cell-matrix interactions and access to trophic factors; however, the effects of culture configuration on the response to high rate deformation have not been evaluated. We examined cell viability following a defined mechanical insult to primary cortical neurons distributed throughout a bioactive matrix (3-D) or in a monolayer sandwiched between layers of a bioactive matrix (2-D). After high rate loading (20 or 30 sec(-1); 0.50 strain), there was a significant decrease in neuron viability for both configurations versus unloaded control cultures; however, neurons in 3-D presented greater cell death based on matched bulk loading parameters. Computer simulations of bulk loading predicted local cellular strains, revealing that neurons in 3-D were subjected to a heterogeneous strain field simultaneously consisting of tensile, compressive and shear strains; conversely, neurons in 2-D experienced a less complex deformation regime varying mainly based on shear strains. These results show differential susceptibility to mechanical loading between neurons cultured in 2-D and 3-D that may be due to differences in cellular strain manifestation. Models of TBI that accurately represent the related cellular biomechanics and pathophysiology are important for the elucidation of cellular tolerances and the development of mechanistically driven intervention strategies.