Modeling the Effects of Drug Binding on the Dynamic Instability of Microtubules

TL;DR

This paper introduces a stochastic model to analyze how drug binding affects microtubule dynamic instability, focusing on the impact of S-methyl-D-DM1 on microtubule growth and catastrophe processes.

Contribution

It presents a novel stochastic model that incorporates drug effects on microtubule dynamics, specifically highlighting the importance of suppressing GDP tubulin loss for effective drug action.

Findings

S-methyl-D-DM1 suppresses microtubule dynamic instability.

Effective suppression requires inhibiting GDP tubulin loss.

Model aligns with experimental observations.

Abstract

We propose a stochastic model that accounts for the growth, catastrophe and rescue processes of steady state microtubules assembled from MAP-free tubulin. Both experimentally and theoretically we study the perturbation of microtubule dynamic instability by S-methyl-D-DM1, a synthetic derivative of the microtubule-targeted agent maytansine and a potential anticancer agent. We find that to be an effective suppressor of microtubule dynamics a drug must primarily suppress the loss of GDP tubulin from the microtubule tip.