HPC MSU

Publication Abstract

Mechano-physiological Damage Modeling of Neuronal Death Due to Traumatic Brain Injury

Bakhtiary, A., Prabhu, R., Horstemeyer, M., Murphy, M. A., Mun, S., LaPlaca, M. C., & Jones, M. D. (2017). Mechano-physiological Damage Modeling of Neuronal Death Due to Traumatic Brain Injury. International Mechanical Engineering Congress & Exposition. Tampa, FL: American Society of Mechanical Engineers.

Abstract

A centers for disease control and prevention (CDC) report on the increase of sports related traumatic brain injury (TBI) incidents, highlight the need for better protective gear and helmet design. Robust helmet design, for sports purposes, requires accurate constitutive equations to quantify damage in head models. Current brain constitutive models define damage as a mechanical feature. Implementation of a mechano-physiological form of damage in brain simulations can greatly improve the predictability of TBI in finite element (FE) simulations, and thus helmet design. Mechanoporation and the disruption of intracellular homeostasis directly correlate to cell death during TBI, and can be used to add a physiological dimension to these damage models. In this work, mechanoporation and the intracellular homeostasis disruption are quantified through combining the deformation of a representative lipid bilayer with Nernst-Planck diffusion equations. This approach produces a set of mechano-physiological damage evolution equations that quantify cell death and may be defined as a mechano-physiological internal state variable (MP-ISV). A 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) bilayer with water was used as a representative of a neuronal cell membrane, for the MD model. The MD simulator LAMMPS and the CHARMM36 all-atom lipid force field were used for all simulations. Large deformation at a constant von Mises strain rate was applied in two dimensions to implement equibiaxial, non-equibiaxial and strip biaxial loading conditions on the lipid bilayer. The resulting membrane poration was then quantified using OVITO and an in-house MATLAB analysis code, and decomposed to pore nucleation and growth. These results were used to calibrate the novel pore nucleation and growth rates to define mechanical damage in the bilayer. The Nernst-Planck diffusion equations were implemented to produce mechano-physiological damage evolution equations to measure the intracellular homeostasis disruption. The MD simulations showed equibiaxial deformation at a constant von Mises strain rate resulted in the highest pore growth rate and pore nucleation rate. Pore growth rate was seen to be sensitive to strain rate and stress state; while nucleation rate was only sensitive to the stress state. The intracellular homeostasis disruption for a representative neuron cell agreed with experimental results from cell culture deformations. The Introduction of the presented mechano-physiological damage evolution equations as an MP-ISV into a multiscale head model generates a history, strain rate, and stress state dependent variable, acting as a measure for cell death and TBI in finite element simulations.