Modeling microtubule dynamic instability: Microtubule growth, shortening and pause

Microtubules (MTs) are protein polymers found in all eukaryotic cells. They are crucial for normal cell development, providing structural support for the cell and aiding in the transportation of proteins and organelles. In order to perform these functions, MTs go through periods of relatively slow polymerization (growth) and very fast depolymerization (shortening), where the switch from growth to shortening is called a catastrophe and the switch from shortening to growth is called a rescue. Although MT dynamic instability has traditionally been described solely in terms of growth and shortening, MTs have been shown to pause for extended periods of time, however the reason for pausing is not well understood. Here, we present a new mathematical model to describe MT dynamics in terms of growth, shortening, and pausing. Typically, MT dynamics are defined by four key parameters which include the MT growth rate, shortening rate, frequency of catastrophe, and the frequency of rescue. We derive a mathematical expression for the catastrophe frequency in the presence of pausing, as well as expressions to describe the total time that MTs spend in a state of growth and pause. In addition to exploring MT dynamics in a control-like setting, we explore the implicit effect of stabilizing MT associated proteins (MAPs) and stabilizing and destabilizing chemotherapeutic drugs that target MTs on MT dynamics through variations in model parameters.