Surface designs for the control of cell migration

Micro- and nanostructured surfaces are unique platforms to present artificially designed guidance cues to migrating cells. In particular, arrays of patterns combined with image analysis yield ample statistics of cell behaviour that allow modelling and testing of spatio-temporal control mechanisms at the cellular and molecular level. In the last funding period, we studied cells on ring-like tracks and dumbbell-like two-state patterns to characterize motility and invasive behaviour of cancer cell lines in collaboration with projects B02, B04, B08, B11 and B12. In the present proposal, we will advance confined cell migration on two-state patterns and study the role of the connecting channel, the cell shape evolution, and two-cell exchange dynamics. A major goal is to connect dynamic phenotypes to mechanistic models of reaction-diffusion dynamics inside cells and connect the observed non-linear dynamics to cancer-specific expression of microRNAs (miRs) – in particular miR-200c – and myosin motors. We will focus on the spreading of lamellipodia in curvature-inducing topographies within micropatterns. Here, we will particularly explore the spatio-temporal distribution of the motor protein myosin VI (myo6), which was shown to be upregulated in cancer cells and seems to be strongly correlated with invasiveness. Based on our recent findings on myo6-membrane interactions in vitro, we will investigate the role of membrane curvature in actin cytoskeleton remodelling in migrating cells. To this end, cell migration experiments on topologically structured surfaces and 2D mazes (Rädler) will be carried out and compared to in-vitro experiments of myo6 at the single molecule level as well as when interacting with lipid cargo (Veigel). The studies on structured surfaces will be complemented by cell migration and distribution of myo6 in artificial 3D microstructures such as 3D dumbbell cavities and soft clefts in photo-polymerisable hydrogels.