Abstract
Spatiotemporal variations of oxygen concentration affect the cell behaviors that are involved in physiological and pathological events. In our previous study with Dictyostelium discoideum (Dd) as a model of cell motility, aggregations of Dd cells exhibited long-lasting and highly stable migration in a self-generated hypoxic environment, forming a ring shape that spread toward the outer higher oxygen region. However, it is still unclear what kinds of changes in the migratory properties are responsible for the observed phenomena. Here, we investigated the migration of Dd to clarify the oxygen-dependent characteristics of aerokinesis and aerotaxis. Migratory behaviors of Dd cells were analyzed under various oxygen concentration gradients and uniform oxygen conditions generated in microfluidic devices. Under hypoxic conditions below 2% O2, corresponding to less than 25 µM O2 in the culture medium, the migration of Dd cells was enhanced (aerokinesis) and the oxygen gradient guided the cells toward the oxygen-rich region (aerotaxis). The aerotaxis was attributed to the increase in the frequency of migration associated with the direction of higher O2, the acceleration of migration velocity, and the enhancement of migration straightness. Thus, aerokinesis and aerotaxis are dependent on both the oxygen level and possibly relative gradient and are essential mechanisms for the migration of Dd.
Highlights
Oxygen is essential for many living organisms to generate energy [1]
The cell motility that varies with the oxygen environment is categorized into two modes: random movement with an oxygen-dependent magnitude is called “aerokinesis”, while directed movement attracted by oxygen is called “aerotaxis”
With the help of several models, we proposed that self-generated oxygen gradients depend on the interplay between cell motility, cell division and aerotaxis, rather than cell-cell interactions
Summary
Oxygen concentrations in vivo are lower than those in the atmosphere due to oxygen consumption by cells, and they change spatiotemporally [2]. The spatiotemporal variations of oxygen concentration affect cell behaviors that are involved in physiological and pathological events [3,4]. Macrophages are known to aggregate to an inflammatory hypoxic region through immune reactions [6]. Cancer cells change their characteristics and migratory behaviors by hypoxic exposure [7], which promote metastasis and proliferation [8]. An in vitro study reported the remarkable oxygendirected migration of epithelial cells under a self-generated hypoxic environment as a result of cellular oxygen consumption in a confined environment [9]. Aerotaxis is a phenomenon that is well known in bacteria [10]
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