We present CAMDLES (CFD-DEM Artificial Microgravity Developments for Living Ecosystem Simulation), an extension of CFDEM®Coupling to model biological flows, growth, and mass transfer in artificial microgravity devices. For microbes that accompany humans into space, microgravity-induced alterations in the fluid environment are likely to be a major factor in the microbial experience of spaceflight. Computational modeling is needed to investigate how well ground-based microgravity simulation methods replicate that experience. CAMDLES incorporates agent-based modeling to study inter-species metabolite transport within microbial communities in rotating wall vessel bioreactors (RWVs). Preexisting CFD modeling of RWVs has not yet incorporated growth; CAMDLES employs the simultaneous modeling of biological, chemical, and mechanical processes in a micro-scale rotating reference frame environment. Simulation mass transfer calculations were correlated with Monod dynamic parameters to predict relative growth rates between artificial microgravity, spaceflight microgravity, and 1 g conditions. By simulating a microbial model community of metabolically cooperative strains of Escherichia coli and Salmonella enterica, we found that the greatest difference between microgravity and an RWV or 1 g gravity was when species colocalized in dense aggregates. We also investigated the influence of other features of the system on growth, such as spatial distribution, product yields, and diffusivity. Our simulation provides a basis for future laboratory experiments using this community for investigation in artificial microgravity and spaceflight microgravity. More broadly, our development of these models creates a framework for novel hypothesis generation and design of biological experiments with RWVs, coupling the effects of RWV size, rotation rate, and mass transport directly to bacterial growth in microbial communities.
Macrophages exhibit impaired phagocytosis, adhesion, migration, and cytokine production in space, hindering their ability to elicit immune responses. Considering that the combined effect of spaceflight microgravity and radiation is multiscale and multifactorial in nature, it is expected that contradictory findings are common in the field. This theory paper reanalyzes research on the macrophage spaceflight response across multiple timescales from seconds to weeks, and spatial scales from the molecular, intracellular, extracellular, to the physiological. Key findings include time-dependence of both pro-inflammatory activation and integrin expression. Here, we introduce the time-dependent, intracellular localization of MRTF-A as a hypothetical confounder of macrophage activation. We discuss the mechanosensitive MRTF-A/SRF pathway dependence on the actin cytoskeleton/nucleoskeleton, microtubules, membrane mechanoreceptors, hypoxia, oxidative stress, and intracellular/extracellular crosstalk. By adopting a multiscale perspective, this paper provides the first mechanistic answer for a three-decade-old question regarding impaired cytokine secretion in microgravity—and strengthens the connection between the recent advances in mechanobiology, microgravity, and the spaceflight immune response. Finally, we hypothesize MRTF involvement and complications in treating spaceflight-induced cardiovascular, skeletal, and immune disease.
Macrophages exhibit impaired phagocytosis, adhesion, migration, and cytokine production in space, hindering their ability to elicit immune responses. The combined effect of spaceflight microgravity and radiation on macrophage dysfunction is multiscale and multifactorial in nature. However, spaceflight and simulated microgravity experiments often take single-scale approaches. This hypothesis and theory paper reanalyzes research in the macrophage spaceflight response across multiple scales, from the molecular, intracellular, extracellular, to the physiological. Here, we introduce the time-dependent, mechanotransducive MRTF-A/SRF pathway, which depends on intracellular localization, to elucidate seemingly contradictory macrophage responses across time scales. We discuss the MRTF-A/SRF pathway dependence on the actin cytoskeleton/nucleoskeleton, microtubules, mechanosensitive membrane proteins, hypoxia, oxidative stress, and crosstalk with other pathways and cells. By adopting a multiscale perspective, this paper identifies potential mechanisms for adverse macrophage responses and strengthens the connection between microgravity, mechanobiology, and the spaceflight immune response. Finally, we hypothesize MRTF involvement and complications in treating spaceflight-induced cardiovascular, skeletal, and immune disease.
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