CRC 629 A19 - The Role of actin-based protrusions in 2D versus 3D cell migration

Basic data for this project

Description

The protein actin is the main building block of the actin cytoskeleton, which is indispensable for any type of shape change including cell movement. In order to move, cells form different types of surface-projections, such as lamellipodia or filopodia by dynamic actin polymerisation beneath the membrane, a process that is controlled by signal-dependent catalytic machines. An additional form of cell projection into new space is a process called blebbing. Blebs formation requires myosin II activity on pre-existing actin filaments, and is terminated by the onset of polymerisation within the bleb. When grafted onto 2-dimensional substrates, motile invasive cells like fibroblasts and many cancer cells express all different types of actin rich protrusions. The very same cells, when seeded into a 3-dimensional matrix significantly change their morphology and can even switch to so called amoeboid motility, accompanied by blebbing. These transitions are not understood. Despite the fact that all protrusions types are built by different mechanisms, they co-occur at the leading front. An elucidation of the relative contributions of the respective signals, machines and resulting structures to migration in variable environments is the aim of the project proposed here. In the current project we want to address the following questions: Can cells in principle chemotax in 2D (‘mesenchymal’) when either lamellipodia or filopodia are suppressed? Can cells in principle migrate in 3D in the absence of either filopodia or lamellipodia? Can we control the transition between ‘mesenchymal’ and ‘amoeboid’ movement? What are the switches? How are the different types of cell movement and formation of the different actin structures connected to matrix degradation? Finally, how are circular ruffles connected to the ‘invasive potential’ of cells?