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Molecular Mechanobiology in Space and on Earth 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Biology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 10044

Special Issue Editor


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Guest Editor
Institute of Anatomy, Faculty of Medicine, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
Interests: cell biology; gravitational biology and biomechanics; space medicine; space biotechnology
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Mechanobiology is a rapidly growing field of research, particularly interdisciplinary because it combines biology and engineering. Studies concern, on a cellular level, how mechanical forces are sensed and transduced into intra- and intercellular signals, how they regulate cellular processes and homeostasis, and how they are involved in the induction and progression of diseases. Mechanobiology is becoming increasingly relevant to many fields, e.g., cancer biology, vascular biology, tissue formation, and regeneration, and therefore provides valid input to pharmacology as well as sports and rehabilitation medicine and geriatrics.

Whereas our terrestrial environment has been determined by the Earth’s gravitational force for more than four billion years, Space, in contrast, allows research without this omnipresent external force and thus opens up new access to research on mechanobiological processes. Research in space has greatly contributed to our understanding of how cellular architecture, physiological functions or evolutionary processes have adjusted to the gravitational force. Life science in Space has even helped to understand the molecular basis of human diseases.

Access to Space is getting easier and cheaper today, and that makes targeted use of microgravity increasingly interesting as a tool for research, but also for commercial purposes. Because humankind is now entering the age of space exploration and enjoys an unprecedented level of mobility, technological and economical utilization of Space for healthcare and therapy is in reach, and new ideas arising from fundamental research can be brought into the world through entrepreneurship.

The Special Issue aims at collecting the latest scientific results as well as technological developments from all fields of mechanobiology on Earth or in Space. Under this general topic, we are welcoming manuscripts—either original work or review articles—focused on fundamental life and physical sciences, applied sciences, medical applications, new technologies, new visions that include commercial applications, as well as new or controversial paradigms.

Prof. Dr. Oliver Ullrich
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • microgravity
  • mechanotransduction
  • signal transduction
  • adaptation
  • homeostasis
  • research technologies
  • manufacturing
  • commercial applications

Published Papers (4 papers)

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Research

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29 pages, 6205 KiB  
Article
Transcriptional Response in Human Jurkat T Lymphocytes to a near Physiological Hypergravity Environment and to One Common in Routine Cell Culture Protocols
by Christian Vahlensieck, Cora Sandra Thiel, Meret Mosimann, Timothy Bradley, Fabienne Caldana, Jennifer Polzer, Beatrice Astrid Lauber and Oliver Ullrich
Int. J. Mol. Sci. 2023, 24(2), 1351; https://doi.org/10.3390/ijms24021351 - 10 Jan 2023
Cited by 2 | Viewed by 1582
Abstract
Cellular effects of hypergravity have been described in many studies. We investigated the transcriptional dynamics in Jurkat T cells between 20 s and 60 min of 9 g hypergravity and characterized a highly dynamic biphasic time course of gene expression response with a [...] Read more.
Cellular effects of hypergravity have been described in many studies. We investigated the transcriptional dynamics in Jurkat T cells between 20 s and 60 min of 9 g hypergravity and characterized a highly dynamic biphasic time course of gene expression response with a transition point between rapid adaptation and long-term response at approximately 7 min. Upregulated genes were shifted towards the center of the nuclei, whereby downregulated genes were shifted towards the periphery. Upregulated gene expression was mostly located on chromosomes 16–22. Protein-coding transcripts formed the majority with more than 90% of all differentially expressed genes and followed a continuous trend of downregulation, whereas retained introns demonstrated a biphasic time-course. The gene expression pattern of hypergravity response was not comparable with other stress factors such as oxidative stress, heat shock or inflammation. Furthermore, we tested a routine centrifugation protocol that is widely used to harvest cells for subsequent RNA analysis and detected a huge impact on the transcriptome compared to non-centrifuged samples, which did not return to baseline within 15 min. Thus, we recommend carefully studying the response of any cell types used for any experiments regarding the hypergravity time and levels applied during cell culture procedures and analysis. Full article
(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth 2.0)
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19 pages, 4075 KiB  
Article
Rapid Downregulation of H3K4me3 Binding to Immunoregulatory Genes in Altered Gravity in Primary Human M1 Macrophages
by Christian Vahlensieck, Cora Sandra Thiel, Swantje Christoffel, Sabrina Herbst, Jennifer Polzer, Beatrice Astrid Lauber, Saskia Wolter, Liliana Elisabeth Layer, Jochen Hinkelbein, Svantje Tauber and Oliver Ullrich
Int. J. Mol. Sci. 2023, 24(1), 603; https://doi.org/10.3390/ijms24010603 - 29 Dec 2022
Cited by 1 | Viewed by 1753
Abstract
The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this [...] Read more.
The sensitivity of human immune system cells to gravity changes has been investigated in numerous studies. Human macrophages mediate innate and thus rapid immune defense on the one hand and activate T- and B-cell-based adaptive immune response on the other hand. In this process they finally act as immunoeffector cells, and are essential for tissue regeneration and remodeling. Recently, we demonstrated in the human Jurkat T cell line that genes are differentially regulated in cluster structures under altered gravity. In order to study an in vivo near system of immunologically relevant human cells under physically real microgravity, we performed parabolic flight experiments with primary human M1 macrophages under highly standardized conditions and performed chromatin immunoprecipitation DNA sequencing (ChIP-Seq) for whole-genome epigenetic detection of the DNA-binding loci of the main transcription complex RNA polymerase II and the transcription-associated epigenetic chromatin modification H3K4me3. We identified an overall downregulation of H3K4me3 binding loci in altered gravity, which were unequally distributed inter- and intrachromosomally throughout the genome. Three-quarters of all affected loci were located on the p arm of the chromosomes chr5, chr6, chr9, and chr19. The genomic distribution of the downregulated H3K4me3 loci corresponds to a substantial extent to immunoregulatory genes. In microgravity, analysis of RNA polymerase II binding showed increased binding to multiple loci at coding sequences but decreased binding to central noncoding regions. Detection of altered DNA binding of RNA polymerase II provided direct evidence that gravity changes can lead to altered transcription. Based on this study, we hypothesize that the rapid transcriptional response to changing gravitational forces is specifically encoded in the epigenetic organization of chromatin. Full article
(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth 2.0)
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20 pages, 3844 KiB  
Article
Adaptation and Changes in Actin Dynamics and Cell Motility as Early Responses of Cultured Mammalian Cells to Altered Gravitational Vector
by Zhenlin Ju, Tamlyn N. Thomas, Yi-Jen Chiu, Sakuya Yamanouchi, Yukari Yoshida, Jun-ichi Abe, Akihisa Takahashi, Jing Wang, Keigi Fujiwara and Megumi Hada
Int. J. Mol. Sci. 2022, 23(11), 6127; https://doi.org/10.3390/ijms23116127 - 30 May 2022
Cited by 3 | Viewed by 2025
Abstract
Cultured mammalian cells have been shown to respond to microgravity (μG), but the molecular mechanism is still unknown. The study we report here is focused on molecular and cellular events that occur within a short period of time, which may be related to [...] Read more.
Cultured mammalian cells have been shown to respond to microgravity (μG), but the molecular mechanism is still unknown. The study we report here is focused on molecular and cellular events that occur within a short period of time, which may be related to gravity sensing by cells. Our assumption is that the gravity-sensing mechanism is activated as soon as cells are exposed to any new gravitational environment. To study the molecular events, we exposed cells to simulated μG (SμG) for 15 min, 30 min, 1 h, 2 h, 4 h, and 8 h using a three-dimensional clinostat and made cell lysates, which were then analyzed by reverse phase protein arrays (RPPAs) using a panel of 453 different antibodies. By comparing the RPPA data from cells cultured at 1G with those of cells under SμG, we identified a total of 35 proteomic changes in the SμG samples and found that 20 of these changes took place, mostly transiently, within 30 min. In the 4 h and 8 h samples, there were only two RPPA changes, suggesting that the physiology of these cells is practically indistinguishable from that of cells cultured at 1 G. Among the proteins involved in the early proteomic changes were those that regulate cell motility and cytoskeletal organization. To see whether changes in gravitational environment indeed activate cell motility, we flipped the culture dish upside down (directional change in gravity vector) and studied cell migration and actin cytoskeletal organization. We found that compared with cells grown right-side up, upside-down cells transiently lost stress fibers and rapidly developed lamellipodia, which was supported by increased activity of Ras-related C3 botulinum toxin substrate 1 (Rac1). The upside-down cells also increased their migratory activity. It is possible that these early molecular and cellular events play roles in gravity sensing by mammalian cells. Our study also indicated that these early responses are transient, suggesting that cells appear to adapt physiologically to a new gravitational environment. Full article
(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth 2.0)
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Review

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20 pages, 1500 KiB  
Review
Potential Roles of YAP/TAZ Mechanotransduction in Spaceflight-Induced Liver Dysfunction
by Wang Li, Xinyu Shu, Xiaoyu Zhang, Ziliang Zhang, Shujin Sun, Ning Li and Mian Long
Int. J. Mol. Sci. 2023, 24(3), 2197; https://doi.org/10.3390/ijms24032197 - 22 Jan 2023
Cited by 3 | Viewed by 3544
Abstract
Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, [...] Read more.
Microgravity exposure during spaceflight causes the disordered regulation of liver function, presenting a specialized mechano-biological coupling process. While YAP/TAZ serves as a typical mechanosensitive pathway involved in hepatocyte metabolism, it remains unclear whether and how it is correlated with microgravity-induced liver dysfunction. Here, we discussed liver function alterations induced by spaceflight or simulated effects of microgravity on Earth. The roles of YAP/TAZ serving as a potential bridge in connecting liver metabolism with microgravity were specifically summarized. Existing evidence indicated that YAP/TAZ target gene expressions were affected by mechanotransductive pathways and phase separation, reasonably speculating that microgravity might regulate YAP/TAZ activation by disrupting these pathways via cytoskeletal remodeling or nuclear deformation, or disturbing condensates formation via diffusion limit, and then breaking liver homeostasis. Full article
(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth 2.0)
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