The Dynamics of Aerotaxis in a Simple Eukaryotic Model

In aerobic organisms, oxygen is essential for efficient energy production, acting as the last acceptor of the mitochondrial electron transport chain and as regulator of gene expression. However, excessive oxygen can lead to production of deleterious reactive oxygen species. Therefore, the directed migration of single cells or cell clumps from hypoxic areas towards a region of optimal oxygen concentration, named aerotaxis, can be considered an adaptive mechanism, playing a major role in biological and pathological processes. One relevant example is the development of O2 gradients when tumors grow beyond their vascular supply, leading frequently to metastasis. In higher eukaryotic organisms aerotaxis has only recently begun to be explored, but genetically amenable model organisms suitable to dissect this process remain an unmet need. In this regard, we sought to assess whether Dictyostelium cells, which are an established model for chemotaxis and other motility processes, could sense oxygen gradients and move directionally in their response. By assessing different physical parameters, our findings indicate that both growing and starving Dictyostelium cells under hypoxic conditions migrate directionally towards regions of higher O2 concentration. This migration is characterized by a specific pattern of cell arrangement. A thickened circular front of high cell density (corona) forms in the cell cluster and persistently moves following the oxygen gradient. Cells in the colony center, where hypoxia is more severe, are less motile and display a rounded shape. Aggregation-competent cells forming streams by chemotaxis, when confined under hypoxic conditions, undergo stream or aggregate fragmentation, giving rise to multiple small loose aggregates that coordinately move towards regions of higher O2 concentration. By testing a panel of mutants, defective in chemotactic signaling, and a catalase deficient strain, we found that the latter and the pkbR1null exhibited altered migration patterns aerotactic behavior. Overall oOOur results suggest that in Dictyostelium, like in mammalian cells, require an intracellular accumulation of hydrogen peroxide that triggers favors the migration towards optimal oxygen concentration. Furthermore, differently from chemotaxis, this oxygen-driven migration aerotaxis is a G protein independent process.