Open AccessMorphological and Molecular Changes in Juvenile Normal Human Fibroblasts Exposed to Simulated Microgravity
Author(s) -
Christoph Buken,
Jayashree Sahana,
Thomas J. Corydon,
Daniela Melnik,
Johann Bauer,
Markus Wehland,
Marcus Krüger,
Silke Balk,
Nauras Abuagela,
Manfred Infanger,
Daniela Grimm
Publication year - 2019
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-019-48378-9
Subject(s) - focal adhesion , microbiology and biotechnology , fibronectin , cytoskeleton , extracellular matrix , laminin , actin cytoskeleton , vimentin , cell adhesion , wound healing , integrin , biology , chemistry , cell , signal transduction , immunology , biochemistry , immunohistochemistry
The literature suggests morphological alterations and molecular biological changes within the cellular milieu of human cells, exposed to microgravity (µ g ), as many cell types assemble to multicellular spheroids (MCS). In this study we investigated juvenile normal human dermal fibroblasts (NHDF) grown in simulated µ g (s-µ g ) on a random positioning machine (RPM), aiming to study changes in cell morphology, cytoskeleton, extracellular matrix (ECM), focal adhesion and growth factors. On the RPM, NHDF formed an adherent monolayer and compact MCS. For the two cell populations we found a differential regulation of fibronectin, laminin, collagen-IV, aggrecan, osteopontin, TIMP-1, integrin-β 1 , caveolin-1, E-cadherin, talin-1, vimentin, α-SM actin, TGF-β 1 , IL-8, MCP-1, MMP-1, and MMP-14 both on the transcriptional and/or translational level. Immunofluorescence staining revealed only slight structural changes in cytoskeletal components. Flow cytometry showed various membrane-bound proteins with considerable variations. In silico analyses of the regulated proteins revealed an interaction network, contributing to MCS growth via signals mediated by integrin-β 1 , E-cadherin, caveolin-1 and talin-1. In conclusion, s-µ g -conditions induced changes in the cytoskeleton, ECM, focal adhesion and growth behavior of NHDF and we identified for the first time factors involved in fibroblast 3D-assembly. This new knowledge might be of importance in tissue engineering, wound healing and cancer metastasis.