High altitude and many diseases (e.g. cardiovascular diseases, cancer and chronic wounds) are associated with a limited oxygen supply. Cells can adapt to hypoxia by various mechanisms. Yet, the effects of hypoxia on cell morphology and the actin cytoskeleton are largely unknown. Here we present a comprehensive examination of the cell architecture and function of L929 fibroblasts and C2C12 myoblasts under hypoxic conditions (1% O₂). Cells cultivated in an hypoxic environment show striking morphological differences compared to cells cultivated under normoxic conditions, including an enlargement of cell size, changing cell protrusions, increased numbers of focal contacts, loss of cell polarization and a b- and g -actin redistribution. In L929 fibroblasts these changes go along with enhanced cell spreading and a decline of cell motility in wound closure assays and single cell motility assays.

The hypoxia inducible factor -1a (HIF-1a) is stabilized in hypoxia and plays a pivotal role in the response to changes in oxygen availability. Using a siRNA-approach we show, however, that the observed cellular hypoxic changes are independent of HIF-1a. If the oxygen dependent prolyl-4-hydroxylase domain enzymes (PHDs) are engaged in the hypoxic alterations and how the small GTPases RhoA, RhoC, Rac and Cdc42 are involved is currently under investigation.