Abstract
In this manuscript, we have studied the microstructure of the axonal cytoskeleton and adopted a bottom-up approach to evaluate the mechanical responses of axons. The cytoskeleton of the axon includes the microtubules (MT), Tau proteins (Tau), neurofilaments (NF), and microfilaments (MF). Although most of the rigidity of the axons is due to the MT, the viscoelastic response of axons comes from the Tau. Early studies have shown that NF and MF do not provide significant elasticity to the overall response of axons. Therefore, the most critical aspect of the mechanical response of axons is the microstructural topology of how MT and Tau are connected and construct the cross-linked network. Using a scanning electron microscope (SEM), the cross-sectional view of the axons revealed that the MTs are organized in a hexagonal array and cross-linked by Tau. Therefore, we have developed a hexagonal Representative Volume Element (RVE) of the axonal microstructure with MT and Tau as fibers. The matrix of the RVE is modeled by considering a combined effect of NF and MF. A parametric study is done by varying fiber geometric and mechanical properties. The Young's modulus and spacing of MT are varied between 1.5 and 1.9 GPa and 20-38 nm, respectively. Tau is modeled as a 3-parameter General Maxwell viscoelastic material. The failure strains for MT and Tau are taken to be 50 and 40%, respectively. A total of 4 RVEs are prepared for finite element analysis, and six loading cases are inspected to quantify the three-dimensional (3D) viscoelastic relaxation response. The volume-averaged stress and strain are then used to fit the relaxation Prony series. Next, we imposed varying strain rates (between 10/sec to 50/sec) on the RVE and analyzed the axonal failure process. We have observed that the 40% failure strain of Tau is achieved in all strain rates before the MT reaches its failure strain of 50%. The corresponding axonal failure strain and stress vary between 6 and 11% and 5-19.8 MPa, respectively. This study can be used to model macroscale axonal aggregate typical of the white matter region of the brain tissue.