A synthetic biochemical device for sensing microgravity (original) (raw)
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Advantages and Limitations of Current Microgravity Platforms for Space Biology Research
Applied Sciences
Human Space exploration has created new challenges and new opportunities for science. Reaching beyond the Earth’s surface has raised the issue of the importance of gravity for the development and the physiology of biological systems, while giving scientists the tools to study the mechanisms of response and adaptation to the microgravity environment. As life has evolved under the constant influence of gravity, gravity affects biological systems at a very fundamental level. Owing to limited access to spaceflight platforms, scientists rely heavily on on-ground facilities that reproduce, to a different extent, microgravity or its effects. However, the technical constraints of counterbalancing the gravitational force on Earth add complexity to data interpretation. In-flight experiments are also not without their challenges, including additional stressors, such as cosmic radiation and lack of convection. It is thus extremely important in Space biology to design experiments in a way that m...
Nature Microgravity, 2019
Cells in simulated microgravity undergo a reversible morphology switch, causing the appearance of two distinct phenotypes. Despite the dramatic splitting into an adherent-fusiform and a floating-spherical population, when looking at the gene-expression phase space, cell transition ends up in a largely invariant gene transcription profile characterized by only mild modifications in the respective Pearson's correlation coefficients. Functional changes among the different phenotypes emerging in simulated microgravity using random positioning machine are adaptive modifications-as cells promptly recover their native phenotype when placed again into normal gravity-and do not alter the internal gene coherence. However, biophysical constraints are required to drive phenotypic commitment in an appropriate way, compatible with physiological requirements, given that absence of gravity foster cells to oscillate between different attractor states, thus preventing them to acquire a exclusive phenotype. This is a proof-of-concept of the adaptive properties of gene-expression networks supporting very different phenotypes by coordinated 'profile preserving' modifications. npj Microgravity (2019) 5:27 ; https://doi.org/10.1038/s41526-019-0088-x INTRODUCTION Living organisms on the surface of the Earth experience dramatic changes when the gravity environment changes from Earth gravity (1g) to microgravity in space. Such changes cover a wide range of biological consequences ranging from microbial growth to immune functions in astronauts. 1 As evidenced by microarray studies, these changes are associated with modifications in gene expression, both in real and simulated microgravity. 2-4 As a result, understanding how and why cells and tissues modify their behaviour and morphology in absence of gravity recently became a new paradigm for widening and deepening our knowledge of the role of constraints in Biology. 5 It is worth noting that human cell types cultured in microgravity undergo dramatic morphology changes, leading to two alternative phenotypes: an 'adherent' and a 'floating cell clumps' one, simultaneously present in the same culture. 6-8 This is a reversible process: when a 'clumps-organoid' population is seeded in normal gravity, it goes back to the usual phenotype and, when reseeded in microgravity condition, it gives rise to the two above-mentioned phenotypes. A similar behaviour is observed when the experiment is reiterated starting with cells obtained from the adherent phenotype. To the best of our knowledge, only one study has investigated the differences in gene expression between the two morphologic phenotypes emerging in micro-gravity. 9 Yet, even in this case, the overall coherence (i.e. the stability of the autocorrelation values among gene expressions along the transition through different phenotypic states) in both phenotypes has never been performed up to now. Here we are focusing on two alternative hypotheses about the relation between morphology/functionality and gene expression. (a) The relaxation of gravity constraint allows the appearance of
Modeling the Impact of Microgravity at the Cellular Level: Implications for Human Disease
Frontiers in Cell and Developmental Biology
A lack of gravity experienced during space flight has been shown to have profound effects on human physiology including muscle atrophy, reductions in bone density and immune function, and endocrine disorders. At present, these physiological changes present major obstacles to long-term space missions. What is not clear is which pathophysiological disruptions reflect changes at the cellular level versus changes that occur due to the impact of weightlessness on the entire body. This review focuses on current research investigating the impact of microgravity at the cellular level including cellular morphology, proliferation, and adhesion. As direct research in space is currently cost prohibitive, we describe here the use of microgravity simulators for studies at the cellular level. Such instruments provide valuable tools for cost-effective research to better discern the impact of weightlessness on cellular function. Despite recent advances in understanding the relationship between extracellular forces and cell behavior, very little is understood about cellular biology and mechanotransduction under microgravity conditions. This review will examine recent insights into the impact of simulated microgravity on cell biology and how this technology may provide new insight into advancing our understanding of mechanically driven biology and disease.
How cells (might) sense microgravity
The FASEB Journal, 1999
This article is a summary of a lecture presented at an ESA/NASA Workshop on Cell and Molecular Biology Research in Space that convened in Leuven, Belgium, in June 1998. Recent studies are reviewed which suggest that cells may sense mechanical stresses, including those due to gravity, through changes in the balance of forces that are transmitted across transmembrane adhesion receptors that link the cytoskeleton to the extracellular matrix and to other cells (e.g., integrins, cadherins, selectins). The mechanism by which these mechanical signals are transduced and converted into a biochemical response appears to be based, in part, on the finding that living cells use a tension-dependent form of architecture, known as tensegrity, to organize and stabilize their cytoskeleton. Because of tensegrity, the cellular response to stress differs depending on the level of pre-stress (pre-existing tension) in the cytoskeleton and it involves all three cytoskeletal filament systems as well as nuclear scaffolds. Recent studies confirm that alterations in the cellular force balance can influence intracellular biochemistry within focal adhesion complexes that form at the site of integrin binding as well as gene expression in the nucleus. These results suggest that gravity sensation may not result from direct activation of any single gravioreceptor molecule. Instead, gravitational forces may be experienced by individual cells in the living organism as a result of stress-dependent changes in cell, tissue, or organ structure that, in turn, alter extracellular matrix mechanics, cell shape, cytoskeletal organization, or internal pre-stress in the cell-tissue matrix.-Ingber, D. How cells (might) sense microgravity. FASEB J. 13 (Suppl.), S3-S15 (1999) Key Words: mechanotransduction ⅐ cytoskeleton ⅐ tensegrity ⅐ integrins ⅐ cell shape This paper is based on an invited lecture I presented at the Belgium National Academy of Sciences in the opening symposium of the European Space Agency (ESA) 2 /National Aeronautics and Space Administration (NASA) Workshop on Cell and Molecular Biology Research in Space, which convened in Leuven, Belgium in June 1998. The organizers chose the title of my lecture: How cells (MIGHT) sense microgravity. The word, "might," was probably added as an afterthought by a wise meeting organizer. This was a prudent choice because although it is clear that physical forces, such as those due to gravity, are fundamental regulators of tissue development, little is known about how living cells sense these signals and convert them into a biochemical response. This transduction process, which is at the core of gravity sensation, is known as mechanotransduction; and this is what I will focus on today. Past work on mechanotransduction has revealed that certain cells have evolved specialized crystal structures that respond directly to the force of gravity. These dense crystals are called statoliths, literally "standing stones," or otoliths, as in the case of the sensory cells of the inner ear. When we move our heads, these dense crystals slide over the receptor cells like tiny lead weights, and it is the resulting localized distortion of the cell surface and interconnected cytoskeleton (CSK) that is somehow sensed by the cell. The statolith represents an elegant mechanism for mechanotransduction, however, it does not explain how all of the cells in the body sense gravity. One of the most common changes observed in astronauts who undergo long-term spaceflight is bone resorption. In fact, it has been known for over a century that bone matrix is deposited in distinct patterns that precisely map out engineering lines of tension and compression for any structure of that size and shape under similar loading conditions (1). If the loading pattern is altered or an astronaut is placed in microgravity, the bone immediately remodels. We now know that living cells within bone (osteoblasts, osteoclasts) are responsible for this remodeling. This means that individual cells must be able to sense changes in physical forces in their local environment that are caused by gravity and that they respond in the most efficient manner possible: by putting new matrix where it is needed and removing
Putative Receptors for Gravity Sensing in Mammalian Cells: The Effects of Microgravity
Applied Sciences
Gravity is a constitutive force that influences life on Earth. It is sensed and translated into biochemical stimuli through the so called “mechanosensors”, proteins able to change their molecular conformation in order to amplify external cues causing several intracellular responses. Mechanosensors are widely represented in the human body with important structures such as otholiths in hair cells of vestibular system and statoliths in plants. Moreover, they are also present in the bone, where mechanical cues can cause bone resorption or formation and in muscle in which mechanical stimuli can increase the sensibility for mechanical stretch. In this review, we discuss the role of mechanosensors in two different conditions: normogravity and microgravity, emphasizing their emerging role in microgravity. Microgravity is a singular condition in which many molecular changes occur, strictly connected with the modified gravity force and free fall of bodies. Here, we first summarize the most im...
Current knowledge about the impact of microgravity on the proteome
Expert Review of Proteomics, 2018
Introduction: Microgravity (µg) is an extreme stressor for plants, animals and humans and influences biological systems. Humans in space experience various health problems during and after a long-term stay in orbit. Various studies have demonstrated alterations in structural and molecular dynamics within the cellular milieu of plants, bacteria, microorganisms, animals and cells. These data were obtained by proteomics investigations applied in gravitational biology to elucidate changes in the proteome occurring when cells or organisms were exposed to real µg (r-µg) and simulated µg (s-µg). Areas covered: In this review, we summarize the current knowledge about the impact of µg on the proteome in plant, animal and human cells. The literature suggests that µg impacts the proteome and thus various biological processes such as angiogenesis, apoptosis, cell adhesion, cytoskeleton, extracellular matrix proteins, migration, proliferation, stress response, and signal transduction. The changes in cellular function depend on the respective cell type. Expert commentary: This data is important for the topics of gravitational biology, tissue engineering, cancer research and translational regenerative medicine. Moreover, it may provide new ideas for countermeasures to protect the health of future space travelers.
Yeast genomic expression patterns in response to low-shear modeled microgravity
2007
The low-shear microgravity environment, modeled by rotating suspension culture bioreactors called high aspect ratio vessels (HARVs), allows investigation in ground-based studies of the effects of microgravity on eukaryotic cells and provides insights into the impact of space flight on cellular physiology. We have previously demonstrated that low-shear modeled microgravity (LSMMG) causes significant phenotypic changes of a select group of Saccharomyces cerevisiae genes associated with the establishment of cell polarity, bipolar budding, and cell separation. However, the mechanisms cells utilize to sense and respond to microgravity and the fundamental gene expression changes that occur are largely unknown. In this study, we examined the global transcriptional response of yeast cells grown under LSMMG conditions using DNA microarray analysis in order to determine if exposure to LSMMG results in changes in gene expression.
Microgravity: A Tool for Protein Drug Development
International Journal of Pharmaceutical Sciences Review and Research
For the past two decades diverse technological advancement in X-ray crystallography have resulted in faster determination of structures of large macromolecules especially proteins. Although the capacity to produce diffraction-quality crystals suitable for exhaustive structural analysis remains a bottleneck, even with the combined automated technology cum site directed mutagenesis. Research in the crystallization of protein in microgravity promises to proffer solution to some of the grey areas as crystals of better quality are produced in the microgravity compared to the Earth's environment. This is used extensively in drug development especially monoclonal antibodies (MABs); and in other applications has been acknowledged by some group of scientists and those of the International Space Station (ISS). This paper recapitulates the account of some of the work done by these scientists on protein crystals yielded in microgravity and the application of the crystals in MABs drug development and other important areas.
How and why does the proteome respond to microgravity?
Expert Review of Proteomics, 2011
For medical and biotechnological reasons, it is important to study mammalian cells, animals, bacteria and plants exposed to simulated and real microgravity. It is necessary to detect the cellular changes that cause the medical problems often observed in astronauts, cosmonauts or animals returning from prolonged space missions. In order for in vitro tissue engineering under microgravity conditions to succeed, the features of the cell that change need to be known. In this article, we summarize current knowledge about the effects of microgravity on the proteome in different cell types. Many studies suggest that the effects of microgravity on major cell functions depend on the responding cell type. Here, we discuss and speculate how and why the proteome responds to microgravity, focusing on proteomic discoveries and their future potential.