Mechanical Properties Of Microtubules Under Various Chemical Conditions

Microtubules are stiff and dynamic cytoskeletal filaments that play important roles in intracellular transport, intracellular force generation, and cell division. Many chemotherapeutic drugs inhibit microtubules’ dynamics in order to prevent tumor cells from dividing. However, due to the lack of fundamental understanding of the mechanical and structural changes of microtubules induced by chemotherapeutic drugs, scientists are still unable to minimize the side effects associated with chemotherapy. Thus, in this project, we aim to understand the synergetic effects of taxol, a microtubule stabilizer that is commonly used as a chemotherapeutic drug, and tau proteins, which not only stabilize microtubules but are critical to the development of healthy nervous system, on the mechanical properties of microtubules. To study the mechanical properties of microtubules, we record movies of microtubules’ thermal fluctuations and analyze their stiffness by fitting the contour of microtubules with orthogonal polynomials and further obtain the persistence length of the microtubule using the worm-like chain model. From previous study, it was found that tau proteins have little to no effect on the stiffness of microtubules if coated after the microtubules are polymerized with the presence of taxol. However, we have found that the stiffness of tau proteins assembled microtubules is significantly higher than taxol assembled microtubules. The result suggests that taxol might induce significant structural and mechanical changes on microtubules that are overriding tau proteins’ effects on microtubules. This finding could lead us to gain a better understanding of the effects of taxol on microtubules’ mechanical properties on a molecular level.