Rapid adaptation to microgravity in mammalian macrophage cells

Abstract

Despite the observed severe effects of microgravity on mammalian cells, many astronauts have completed long term stays in space without suffering from severe health problems. This raises questions about the cellular capacity for adaptation to a new gravitational environment. The International Space Station (ISS) experiment TRIPLE LUX A, performed in the BIOLAB laboratory of the ISS COLUMBUS module, allowed for the first time the direct measurement of a cellular function in real time and on orbit. We measured the oxidative burst reaction in mammalian macrophages (NR8383 rat alveolar macrophages) exposed to a centrifuge regime of internal 0 g and 1 g controls and step-wise increase or decrease of the gravitational force in four independent experiments. Surprisingly, we found that these macrophages adapted to microgravity in an ultra-fast manner within seconds, after an immediate inhibitory effect on the oxidative burst reaction. For the first time, we provided direct evidence of cellular sensitivity to gravity, through real-time on orbit measurements and by using an experimental system, in which all factors except gravity were constant. The surprisingly ultra-fast adaptation to microgravity indicates that mammalian macrophages are equipped with a highly efficient adaptation potential to a low gravity environment. This opens new avenues for the exploration of adaptation of mammalian cells to gravitational changes.

Rapid Cellular Perception of Gravitational Forces in Human Jurkat T Cells and Transduction into Gene Expression Regulation

“…Indeed, mechanical force transduction into the chromatin occurs within milliseconds [50], allowing the nuclear structure to respond directly without biochemical signaling [51,52]. In previous studies which have investigated the oxidative burst reaction in mammalian macrophage cells in microgravity, rapid adaption to a microgravity environment was detected in microgravity on board of the ISS [10], but not in the vag of clinorotation experiments [12,53,54].…”

“…If 99% of such pivotal events cannot be simulated by analogous clinostat experiments, the general assumption that 2D clinostats provide a valid simulation of microgravity and can be recommended for most biological organisms [20] should be revised. If in addition the primary trigger of gravity-induced gene expression response [10,46] is less than one second, the fundamental question of suitability of the clinostat system for the investigation of mammalian cells arises. We therefore recommend that sufficient validation experiments should be carried out before starting experiments with vag as simulation for real microgravity.…”

“…The human organism reacts and partially adapts to altered gravity [2,3] in a time frame of a few hours up to several weeks [4]. The cellular response to microgravity, such as functional alterations [5,6], nucleus size, and shape [7][8][9], and RNA transcription [10,11] mostly occurs within seconds, sometimes months [12][13][14][15]. The question about the mechanism by which gravitational force is transmitted into a biological process was raised decades ago [16,17], but it was rarely addressed in experimental approaches.…”

“…Changes of the gravitational environment induce strong alterations of human physiological systems, which respond and adapt within hours and weeks [44]. At the cellular level, changes of the gravitational force affect morphology, proliferation, differentiation, signal transduction, and gene expression [45] and have been detected within seconds in isolated cells of the immune system [10,12,13,46,47]. We recently investigated the dynamics of gene expression response to different gravitational environments in human Jurkat T lymphocytes in combination of parabolic flights with a suborbital ballistic rocket experiment and with control experiments for excluding all possible other factors of influence [13,14].…”

Cooling the motion of a silica microsphere in a magneto-gravitational trap in ultra-high vacuum

“…This allows for the use of very low light level illumination, avoiding the heating and instability problems that may occur in optical trapping experiments as residual gas pressure is reduced [10,11,16,17]. The static fields and the ubiquity of diamagnetism allow a broad range of materials to be trapped, including living organisms [22], which could enable ground-based studies of the effects of microgravity on cells [23]. Furthermore, the extremely low damping rates of the COM motion in the trap, reported here, could make diamagnetically trapped microspheres particularly valuable for detecting weak forces.…”