4  -  Impact of keratin network regulation on migrating cells

Uniklinik RWTH Aachen (RWTH) - Germany

Student: Anne Pora

Supervisors: Rudolf Leube,  Reinhard Windoffer,  Björn Kampa,  Bernd Hoffmann

Cell migration is a highly complex process, in which physical and chemical signals act on different cellular components. We aim at understanding how the dynamic behavior of the epithelial keratin intermediate filament cyto­skeleton and its associated hemidesmo­somal anchorage sites is integrated in migrating cells and influenced by the mechanical characte­ris­tics of the environment.

Using human primary keratinocytes grown on extracellular matrices of different elasticities, we demonstrate that matrix stiffness affects cell morphology, speed and directionality of migra­tion and keratin intermediate filament turnover. We find that hemidesmosomal components are organized in an ordered fashion in these cells exerting distinct forces on the matrix. We assess the effects of matrix stretching and of con­finement on keratin network dynamics. Our data provide evidence for reorganization of the keratin cytoskeleton and its associated matrix adhesion sites in migrating cells responding to mechanophysical matrix properties.