CYTOSKELETON DISRUPTION EFFECT ON FOCAL ADHESION DYNAMICS

Abstract

This thesis project investigates the changes in Focal Adhesions (FAs) dynamics following the disruption of the cytoskeleton components. FAs are necessary protein complexes in chemical signaling, mechanical force transmission, and cell migration. Focal adhesion occurs in protrusion sites by assembling integrin and mechanosensory proteins like FAK, talin, and vinculin. Despite numerous studies available about the interaction of focal adhesion proteins with each other, little detail is known about how the cytoskeleton components influence the lifetime, area, translocation, and formation frequency of focal adhesion. Chemotherapy is the most common cancer treatment. Pharmacological agents such as nocodazole, latrunculin B, and cytochalasin D are known to influence the cytoskeleton components of the cell and are applied in the laboratory. The interaction of the cytoskeleton with focal adhesions is crucial for many cellular processes, including motility and cell adhesion. Thus, given the influence of focal adhesion on the cytoskeleton, studying the effect of these drugs on cell migration could contribute to the development of therapies against tumor growth. In our study, we show that adding nocodazole changes the behavior of cells. Moreover, microtubule depolymerization alters the dynamics of focal adhesions by increasing their area and decreasing their lifetime. Furthermore, disruption of microfilaments with 0.5 μM latrunculin B and 0.5 μM cytochalasin D significantly inhibits cell migration. Furthermore, these actin filament inhibitors substantially reduce the translocation and formation of focal adhesions at the edges of the cell.