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Molecular Mechanobiology in Space and on Earth

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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 (31 May 2021) | Viewed by 17544

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Prof. Dr. Oliver Ullrich

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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

Prof. Dr. Marcel Egli

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Guest Editor

Lucerne University of Applied Sciences and Arts, Luzern (HSLU), Head Institute of Medical Engineering, Space Biology Group, Switzerland
Interests: Cell Biology; Mechanobiology; Biotechnology; Instruments for microgravity research

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. Dr. Oliver Ullrich
Prof. Dr. Marcel Egli
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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

29 pages, 8043 KiB

Open AccessArticle

Rapid Transient Transcriptional Adaptation to Hypergravity in Jurkat T Cells Revealed by Comparative Analysis of Microarray and RNA-Seq Data

by Christian Vahlensieck, Cora S. Thiel, Jan Adelmann, Beatrice A. Lauber, Jennifer Polzer and Oliver Ullrich

Int. J. Mol. Sci. 2021, 22(16), 8451; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22168451 - 06 Aug 2021

Cited by 9 | Viewed by 2865

Abstract

Cellular responses to micro- and hypergravity are rapid and complex and appear within the first few seconds of exposure. Transcriptomic analyses are a valuable tool to analyze these genome-wide cellular alterations. For a better understanding of the cellular dynamics upon altered gravity exposure, it is important to compare different time points. However, since most of the experiments are designed as endpoint measurements, the combination of cross-experiment meta-studies is inevitable. Microarray and RNA-Seq analyses are two of the main methods to study transcriptomics. In the field of altered gravity research, both methods are frequently used. However, the generation of these data sets is difficult and time-consuming and therefore the number of available data sets in this research field is limited. In this study, we investigated the comparability of microarray and RNA-Seq data and applied the results to a comparison of the transcriptomics dynamics between the hypergravity conditions during two real flight platforms and a centrifuge experiment to identify temporal adaptation processes. We performed a comparative study on an Affymetrix HTA2.0 microarray and a paired-end RNA-Seq data set originating from the same Jurkat T cell RNA samples from a short-term hypergravity experiment. The overall agreeability was high, with better sensitivity of the RNA-Seq analysis. The microarray data set showed weaknesses on the level of single upregulated genes, likely due to its normalization approach. On an aggregated level of biotypes, chromosomal distribution, and gene sets, both technologies performed equally well. The microarray showed better performance on the detection of altered gravity-related splicing events. We found that all initially altered transcripts fully adapted after 15 min to hypergravity and concluded that the altered gene expression response to hypergravity is transient and fully reversible. Based on the combined multiple-platform meta-analysis, we could demonstrate rapid transcriptional adaptation to hypergravity, the differential expression of the ATPase subunits ATP6V1A and ATP6V1D, and the cluster of differentiation (CD) molecules CD1E, CD2AP, CD46, CD47, CD53, CD69, CD96, CD164, and CD226 in hypergravity. We could experimentally demonstrate that it is possible to develop methodological evidence for the meta-analysis of individual data. Full article

(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth)

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31 pages, 11944 KiB

Open AccessArticle

Metabolic Dynamics in Short- and Long-Term Microgravity in Human Primary Macrophages

by Cora S. Thiel, Christian Vahlensieck, Timothy Bradley, Svantje Tauber, Martin Lehmann and Oliver Ullrich

Int. J. Mol. Sci. 2021, 22(13), 6752; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22136752 - 23 Jun 2021

Cited by 7 | Viewed by 2716

Abstract

Microgravity acts on cellular systems on several levels. Cells of the immune system especially react rapidly to changes in gravity. In this study, we performed a correlative metabolomics analysis on short-term and long-term microgravity effects on primary human macrophages. We could detect an increased amino acid concentration after five minutes of altered gravity, that was inverted after 11 days of microgravity. The amino acids that reacted the most to changes in gravity were tightly clustered. The observed effects indicated protein degradation processes in microgravity. Further, glucogenic and ketogenic amino acids were further degraded to Glucose and Ketoleucine. The latter is robustly accumulated in short-term and long-term microgravity but not in hypergravity. We detected highly dynamic and also robust adaptative metabolic changes in altered gravity. Metabolomic studies could contribute significantly to the understanding of gravity-induced integrative effects in human cells. Full article

(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth)

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12 pages, 4947 KiB

Open AccessArticle

Engineered Microvessel for Cell Culture in Simulated Microgravity

by Mei ElGindi, Ibrahim Hamed Ibrahim, Jiranuwat Sapudom, Anna Garcia-Sabate and Jeremy C.M. Teo

Int. J. Mol. Sci. 2021, 22(12), 6331; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22126331 - 13 Jun 2021

Cited by 5 | Viewed by 5413

Abstract

As the number of manned space flights increase, studies on the effects of microgravity on the human body are becoming more important. Due to the high expense and complexity of sending samples into space, simulated microgravity platforms have become a popular way to study these effects on earth. In addition, simulated microgravity has recently drawn the attention of regenerative medicine by increasing cell differentiation capability. These platforms come with many advantages as well as limitations. A main limitation for usage of these platforms is the lack of high-throughput capability due to the use of large cell culture vessels. Therefore, there is a requirement for microvessels for microgravity platforms that limit waste and increase throughput. In this work, a microvessel for commercial cell culture plates was designed. Four 3D printable (polycarbonate (PC), polylactic acid (PLA) and resin) and castable (polydimethylsiloxane (PDMS)) materials were assessed for biocompatibility with adherent and suspension cell types. PDMS was found to be the most suitable material for microvessel fabrication, long-term cell viability and proliferation. It also allows for efficient gas exchange, has no effect on cell culture media pH and does not induce hypoxic conditions. Overall, the designed microvessel can be used on simulated microgravity platforms as a method for long-term high-throughput biomedical studies. Full article

(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth)

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14 pages, 4724 KiB

Open AccessArticle

Scalable Microgravity Simulator Used for Long-Term Musculoskeletal Cells and Tissue Engineering

by Alessandra Cazzaniga, Fabian Ille, Simon Wuest, Carsten Haack, Adrian Koller, Christina Giger-Lange, Monica Zocchi, Marcel Egli, Sara Castiglioni and Jeanette A. Maier

Int. J. Mol. Sci. 2020, 21(23), 8908; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238908 - 24 Nov 2020

Cited by 7 | Viewed by 5601

Abstract

We introduce a new benchtop microgravity simulator (MGS) that is scalable and easy to use. Its working principle is similar to that of random positioning machines (RPM), commonly used in research laboratories and regarded as one of the gold standards for simulating microgravity. The improvement of the MGS concerns mainly the algorithms controlling the movements of the samples and the design that, for the first time, guarantees equal treatment of all the culture flasks undergoing simulated microgravity. Qualification and validation tests of the new device were conducted with human bone marrow stem cells (bMSC) and mouse skeletal muscle myoblasts (C2C12). bMSC were cultured for 4 days on the MGS and the RPM in parallel. In the presence of osteogenic medium, an overexpression of osteogenic markers was detected in the samples from both devices. Similarly, C2C12 cells were maintained for 4 days on the MGS and the rotating wall vessel (RWV) device, another widely used microgravity simulator. Significant downregulation of myogenesis markers was observed in gravitationally unloaded cells. Therefore, similar results can be obtained regardless of the used simulated microgravity devices, namely MGS, RPM, or RWV. The newly developed MGS device thus offers easy and reliable long-term cell culture possibilities under simulated microgravity conditions. Currently, upgrades are in progress to allow real-time monitoring of the culture media and liquids exchange while running. This is of particular interest for long-term cultivation, needed for tissue engineering applications. Tissue grown under real or simulated microgravity has specific features, such as growth in three-dimensions (3D). Growth in weightlessness conditions fosters mechanical, structural, and chemical interactions between cells and the extracellular matrix in any direction. Full article

(This article belongs to the Special Issue Molecular Mechanobiology in Space and on Earth)

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