The effect of microtubule disruption on cell attachment dynamics





Cell - extracellular matrix (ECM) adhesion is an important feature of cells in multicellular organisms which play essential role in development, tissue remodeling and cancer metastasis. It is known that cancer cells treated with microtubule-disrupting drugs such as nocodazole and navelbine activates the integrin-dependent signaling cascade which lead to the assembly of matrix adhesions and increase in cell contractility with the result of enhancement in cell adhesion. Also, it was proposed that the possible mechanism of cell attachment alteration by microtubule disruption is mediated by integrins and not by quantitative changes in number of integrins. Increase in lateral mobility of beta 2 integrins after microtubule disruption and stabilization supports the idea that microtubules can rearrange integrins during integrin-mediated adhesion process. Induced membrane blebbing after microtubule disruption was also proposed as a possible reason of cell attachment alteration due to the fact that these process increases the number of contact sites. However, due to the reason that all the experiments on cell attachment were static and based on fixed cells, it is little known about the role of microtubule disruption in promoting cell attachment dynamics and whether this effect occurs due to increased membrane blebbing induction. Thus, this project focuses on studying the effect of microtubule disruption and membrane blebbing on initial cell attachment dynamics by conducting experiments using microtubule-inhibiting drugs, non-muscle myosin II inhibitor and time-lapse microscopy.