Mechanical Loading of Neurons and Astrocytes with Application to Blast Traumatic Brain Injury

Investigations of the mechanical properties of cells are essential for linking mechanical deformation and loading to injury mechanisms at the cellular level. This is especially important when studying traumatic brain injury (TBI). Neurons and astrocytes are susceptible to damage mechanisms arising from various loading scenarios, ranging from motor vehicle accidents to sports injuries and pressure waves generated by explosions. Obtaining the mechanical properties of cells of the central nervous system (CNS) is a critical step for the development of hierarchical models and multi-scale simulation tools to elucidate how applied macroscopic loading conditions, such as pressure waves, translate into cell deformation and damage. Here we present atomic force microscopy (AFM) indentation data and finite element simulation results on the mechanical response of single neurons and astrocytes to dynamic loading at large strains. Specific AFM testing protocols were developed to characterize the mechanical behavior of both cortical neurons and astrocytes over a range of indentation rates spanning three orders of magnitude – i.e. 10, 1, and 0.1 μm/s. The response of both cell types showed similar qualitative nonlinear viscoelastic patterns although, quantitatively, some differences were noted between the two CNS cell populations. The rheological data were complemented with geometrical measurements of cell body morphology obtained through bright-field and confocal microscopy images. A constitutive model was developed, enabling quantitative comparisons within and between populations of neurons and astrocytes. The proposed model, built upon previous constitutive model developments carried out at the cortical tissue level, was implemented into a three-dimensional finite element framework. The simulated cell responses were successfully calibrated to the experimental measurements under the selected test conditions. The sets of material parameters extracted via the numerical method for both cell types suggest that astrocytes and neurons exhibit distinct viscoelastic behaviors. The body of experimental measurements and numerical results hereby presented provides a solid, preliminary knowledge base, from which further developments may be pursued to unravel the key mechanical pathways potentially involved in TBI.