Effects of Clinical Dosing Schedule of Paclitaxel on Viscoelasticity of Living PC-12 Cells – Finite Element Analysis

Abstract

Chemotherapy treatment of cancer by paclitaxel often results in peripheral neuropathy which is a main reason for patients to withdraw from therapy and reduce the survival rate Most past researches of chemotherapy induced peripheral neuropathy (CIPN) focused on biochemical field The goal of this thesis is using finite element (FE) method and quasi-linear viscoelasticity (QLV) theory to analyze the indentation of PC-12 cells subjected to in vitro simulations of two clinical paclitaxel doses Mechanical properties of the cells were measured by curve fitting to both QLV theory and a FE model Stress-strain relationship was derived from hyperelastic part for comparison purpose Full 3D cell geometry model was built from confocal microscope immunofluorescences images of the cells QLV results show that apparent Young’s modulus rises at 12 hours then goes down at 18 hours for 3-hr infusion groups and rises at 6 and 18 hour for 24-hr infusion groups Viscous parameter C rises at 6 12 hours and goes down for 3-hr group FE results show that relaxation modulus at cytoplasm changes with the decreasing of paclitaxel concentration while that of the nucleus remains unchanged From the stress-strain results the Young’s moduli of the cytoplasm are lower than that of control groups for both 3-hr and 24-hr infusion groups it implies that cytoplasm gets softer after treated by paclitaxel At nucleus the stiffness rises at 12 hours for the 3-hr infusion groups and rises from 6 to 18 hour for the 24-hr groups In conclusion both stiffness and viscous properties have larger changes in the 3-hr infusion group than the 24-hour group suggesting that the cells were damaged more severely due to short time infusion dosing schedule The soften of paclitaxel treated cytoplasm is consistent with the fact that paclitaxel would disrupt the microtubules of the cell FE simulation results suggest that regarding the peak indentation force the axisymmetric model yield similar results as that of the full 3D model saving the computation effort very much Key words: Biomechanics paclitaxel CIPN quasi-linear viscoelastic theory finite element method 3D model reconstruction AFM confocal microscope

Date of Award	2019
Original language	English
Supervisor	Ming-Shaung Ju (Supervisor)