Mathematical Modeling of Effect Of Microtubule-Targeted Agents On Microtubule Dynamic Instability

Abstract

Microtubule-targeted agents (MTAs), widely used in chemotherapy, are molecules that are able to block cancer cell migration and division. Their effect on microtubule (MT) dynamic instability is measured by their influence on observable parameters of MT dynamics such as growth speed, time-based catastrophe frequency, time-based rescue fre- quency, etc. In this paper, we propose a new mathematical model that is able to reproduce MT dynamics with an appropriate estimation of the main observable parameters. Using the experimental data on paclitaxel effect in presence of EB proteins, we fitted param- eters of the model from several drug concentrations. It enable us to understand which non-observable model parameters are able to reproduce the effect of MTAs and thus to highlight a new potential mechanism of action associated with MTAs effect in presence of EB protein.