Search

With the advancement in reusable rocket propulsion technology, space tourist trips into outer space are now becoming a possibility at a cost-effective rate. As such, astronauts will face a host of health-related challenges, particularly on long-duration space missions where maintaining a balanced healthy microbiome is going to be vital for human survival in space exploration as well as mission success. The human microbiome involves a whole list of micro-organisms that reside in and on the human host, and plays an integral role in keeping the human host healthy. However, imbalances in the microbiome have been directly linked to many human diseases. Research findings have clearly shown that the outer space environment can directly affect the normal microbiome of astronauts when the astronaut is exposed to the microgravity environment. In this study, we show that the simulation of microgravity on earth can mimic the outer space microgravity environment. Staphylococus aureus (S. aureus) was chosen for this study as it is an opportunistic pathogen, which is part of the normal human skin microflora and the nasal passages. This study's results show that S. aureus proliferation was significantly increased under a microgravity environment compared to Earth's gravity conditions, which complements previous work performed on bacteria in the outer space environment in the International Space Station (ISS). This demonstrates that this technology can be utilised here on Earth to mimic the outer space environment and to study challenging health-related questions. This in return saves us the cost on conducting experiments in the ISS and can help advance knowledge at a faster rate and produce countermeasures to mitigate the negative side effects of the hostile outer space environment on humans.

COVID-19 lockdowns in early 2020 reduced human mobility, providing an opportunity to disentangle its effects on animals from those of landscape modifications. Using GPS data, we compared movements and road avoidance of 2300 terrestrial mammals (43 species) during the lockdowns to the same period in 2019. Individual responses were variable with no change in average movements or road avoidance behavior, likely due to variable lockdown conditions. However, under strict lockdowns 10-day 95th percentile displacements increased by 73%, suggesting increased landscape permeability. Animals’ 1-hour 95th percentile displacements declined by 12% and animals were 36% closer to roads in areas of high human footprint, indicating reduced avoidance during lockdowns. Overall, lockdowns rapidly altered some spatial behaviors, highlighting variable but substantial impacts of human mobility on wildlife worldwide.

Mental health care providers’ cultural responsiveness related to athletics is crucial to their clinical care provision for student-athletes on college campuses. However, little research has been conducted in applying a theoretical framework to explore providers’ intentions to provide culturally responsive clinical care to this specific student population. Understanding providers’ perceptions of student-athletes is integral in assuring clinical care provision that is responsive related to the culture of athletics. The purpose of this study was to test a conceptual model that adapted the Theory of Planned Behavior to explore the determinants of providers’ intention to be culturally responsive to the unique needs of collegiate student-athletes. For this study, cultural responsiveness was defined as the cumulative level of a provider’s self-efficacy related to communicating with student-athletes, empathy specific to student-athletes, positive attitudes toward the culture of athletics, and knowledge related to the culture of athletics. Data were collected using an online survey method, and the responses from 153 participants were analyzed using multiple regression analysis. The results indicated that all survey scales were stable and reliable on which to base our data analysis results. Additionally, results suggested that the adapted TPB can be a useful framework in predicting mental health care providers’ intention to be culturally responsive to student-athletes’ unique needs. Implications for research are discussed.

The advancement of microgravity simulators is helping many researchers better understanding the impact of the mechanically unloaded space environment on cellular function and disfunction. However, performing microgravity experiments on Earth, using simulators such as the Random Positioning Machine, introduces some unique practical challenges, including air bubble formation and leakage of growth medium from tissue culture flask and plates, all of which limit research progress. Here, we developed an easy-to-use hybrid biological platform designed with the precision of 3D printing technologies combined with PDMS microfluidic fabrication processes to facilitate reliable and reproducible microgravity cellular experiments. The system has been characterized for applications in the contest of brain cancer research by exposing glioblastoma and endothelial cells to 24 h of simulated microgravity condition to investigate the triggered mechanosensing pathways involved in cellular adaptation to the new environment. The platform demonstrated compatibility with different biological assays, i.e., proliferation, viability, morphology, protein expression and imaging of molecular structures, showing advantages over the conventional usage of culture flask. Our results indicated that both cell types are susceptible when the gravitational vector is disrupted, confirming the impact that microgravity has on both cancer and healthy cells functionality. In particular, we observed deactivation of Yap-1 molecule in glioblastoma cells and the remodeling of VE-Cadherin junctional protein in endothelial cells. The study provides support for the application of the proposed biological platform for advancing space mechanobiology research, also highlighting perspectives and strategies for developing next generation of brain cancer molecular therapies, including targeted drug delivery strategies.

The tissue microenvironment contains a complex assortment of multiple cell types, matrices, and vessel structures, which is difficult to reconstruct in vitro. Here, we demonstrate model tumor microenvironments formed through direct writing of vasculature channels and tumor cell aggregates, within a cell-laden microgel matrix. Photocrosslinkable microgels provide control over local and global mechanics, while enabling the integration of virtually any cell type. Direct writing of a Pluronic sacrificial ink into a stromal cell-microgel suspension is used to form vessel structures for endothelialization, followed by printing of melanoma aggregates. Tumor cells migrate into the prototype vessels as a function of spatial location, thereby providing a measure of invasive potential. The integration of perfusable channels with multiple spatially defined cell types provides new avenues for modelling development and disease, with scope for both fundamental research and drug development efforts.

Ion channels activated by mechanical inputs are important force sensing molecules in a wide array of mammalian cells and tissues. The transient receptor potential channel, TRPV4, is a polymodal, nonselective cation channel that can be activated by mechanical inputs but only if stimuli are applied directly at the interface between cells and their substrate, making this molecule a context-dependent force sensor. However, it remains unclear how TRPV4 is activated by mechanical inputs at the cell-substrate interface, which cell intrinsic and cell extrinsic parameters might modulate the mechanical activation of the channel and how mechanical activation differs from TRPV4 gating in response to other stimuli. Here we investigated the impact of substrate mechanics and cytoskeletal components on mechanically evoked TRPV4 currents and addressed how point mutations associated with TRPV4 phosphorylation and arthropathy influence mechanical activation of the channel. Our findings reveal distinct regulatory modulation of TRPV4 from the mechanically activated ion channel PIEZO1, suggesting the mechanosensitivity of these two channels is tuned in response to different parameters. Moreover, our data demonstrate that the effect of point mutations in TRPV4 on channel activation are profoundly dependent on the gating stimulus.

Glioblastoma multiforme (GBM) is one of the most aggressive malignant brain tumors and urgently requires the development of new therapeutic strategies. In this study, an innovative hybrid in vitro vascularized GBM-on-a-chip model is presented as a strategic integration of microfluidics and 3D bioprinting technologies. The system can recreate the compartmentalized brain tumor microenvironment, comprising the functional blood brain barrier (BBB) and the adjacent 3D perivascular tumor niche, by selectively mimicking physiological shear stress and cell–cell, cell–matrix mechanical interaction. The GBM-on-a-chip model was evaluated under simulated microgravity (µG) condition as a form of mechanical unloading showing a significant cell morphological and mechanotransduction response thereby indicating that gravitational forces play an important role in glioblastoma mechanical regulation. The proposed GBM-on-a-chip represents a meaningful biological tool for further research in cancer mechanobiology and pre-clinical approach in brain tumor therapy.

In recent years, there has been an increasing interest in space exploration, supported by the accelerated technological advancements in the field. This has led to a new potential environment that humans could be exposed to in the very near future, and therefore an increasing request to evaluate the impact this may have on our body, including health risks associated with this endeavor. A critical component in regulating the human pathophysiology is represented by the cardiovascular system, which may be heavily affected in these extreme environments of microgravity and radiation. This mini review aims to identify the impact of microgravity and radiation on the cardiovascular system. Being able to understand the effect that comes with deep space explorations, including that of microgravity and space radiation, may also allow us to get a deeper understanding of the heart and ultimately our own basic physiological processes. This information may unlock new factors to consider with space exploration whilst simultaneously increasing our knowledge of the cardiovascular system and potentially associated diseases.

Mechanomics represents the natural progression of knowledge at the intersection of mechanics and biology with the aim to codify the role of mechanical environment on biological adaptation. Compared to the mapping of the human genome, the challenge of mapping the mechanome remains unsolved. Solving this grand challenge will require both top down and bottom up R&D approaches using experimental and computational tools to visualize and measure adaptation as it occurs. Akin to a mechanical test of a smart material that changes its mechanical properties and local environment under load, stem cells adapt their shape, cytoskeletal architecture, intrinsic mechanical properties, as well as their own niche, through cytoskeletal adaptation as well as up- and down-regulation of structural proteins that modulate their mechanical milieux. Recent advances in live cell imaging allow for unprecedented study and measurements of displacements, shape and volume changes in stem cells, reconfiguring of cytoskeletal machinery (nucleus, cytoskeleton), in response to controlled mechanical forces and stresses applied at cellular boundaries. Coupled with multiphysics computational and virtual power theoretical approaches, these novel experimental approaches enable mechanical testing of stem cells, multicellular templates, and tissues inhabited by stem cells, while the stem cells themselves evolve over time. The novel approach is paving the way to decipher mechanisms of structural and functional adaptation of stem cells in response to controlled mechanical cues. This mini-review outlines integrated approaches and methodologies implemented to date in a series of studies carried out by our consortium. The consortium’s body of work is described in context of current roadblocks in the field and innovative, breakthrough solutions and is designed to encourage discourse and cross disciplinary collaboration in the scientific community.

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.

Mechanoelectrical transduction is a cellular signalling pathway where physical stimuli are converted into electro-chemical signals by mechanically activated ion channels. We describe here the presence of mechanically activated currents in melanoma cells that are dependent on TMEM87a, which we have renamed Elkin1. Heterologous expression of this protein in PIEZO1-deficient cells, that exhibit no baseline mechanosensitivity, is sufficient to reconstitute mechanically activated currents. Melanoma cells lacking functional Elkin1 exhibit defective mechanoelectrical transduction, decreased motility and increased dissociation from organotypic spheroids. By analysing cell adhesion properties, we demonstrate that Elkin1 deletion is associated with increased cell-substrate adhesion and decreased homotypic cell-cell adhesion strength. We therefore conclude that Elkin1 supports a PIEZO1-independent mechanoelectrical transduction pathway and modulates cellular adhesions and regulates melanoma cell migration and cell-cell interactions.