Dynamic Mechanical Load as a Trigger for Growth and Proliferation in Porcine Epithelial Cells

Stefan Kahlert ^{1, 2, 3}

Constanze Nossol ¹

Marcus Krüger ^{2, 3, 4, 5}

Sascha Kopp ^{2, 3, 4, 5, 6}

D. Grimm ^{2, 3, 4, 5, 7}

Simon L Wuest ⁸

Hermann-Josef Rothkötter ^{1, 2, 3}

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Institut für Anatomie, Medizinische Fakultät, Otto von Guericke Universität Magdeburg, Leipziger Str. 44, Haus 43, 39120 Magdeburg, Germany

Research Group "Magdeburger Arbeitsgemeinschaft für Forschung unter Raumfahrt- und Schwerelosigkeitsbedingungen" (MARS), Otto von Guericke University, 39106 Magdeburg, Germany |

Research Group “Magdeburger Arbeitsgemeinschaft für Forschung unter Raumfahrt- und Schwerelosigkeitsbedingungen” (MARS), Otto von Guericke Universität Magdeburg, 39106 Magdeburg, Germany

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Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke University, Universitätsplatz 2, 39106 Magdeburg, Germany |

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Department of Microgravity and Translational Regenerative Medicine, Otto von Guericke Universität Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany

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Core Facility Tissue Engineering, Institut für Chemie, Otto von Guericke Universität Magdeburg, Universitätsplatz 2, 39106 Magdeburg, Germany

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Department of Biomedicine, Aarhus University, Høegh-Guldbergs Gade 10, 8000 Aarhus, Denmark |

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Space Biology Group, Institute of Medical Engineering, Lucerne, School of Engineering and Architecture, Lucerne University of Applied Sciences and Arts, Obermattweg 9, 6052 Hergiswil, NW, Switzerland

Publication type: Journal Article

Publication date: 2025-03-20

MDPI

Journal: Biomolecules

scimago Q1

SJR: 1.179

CiteScore: 9.4

Impact factor: 4.8

ISSN: 2218273X

DOI: 10.3390/biom15030455

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Abstract

The impact of gravity is a basic force determining our existence on Earth. Changes in orientation with respect to the gravity vector trigger alternating mechanical forces on organisms, organs, and cells. In the intestines of mammals, epithelial cells are continuously exposed to changed orientations to gravity. In this study, we employed dynamic cultivation systems to mimic the load changes and the resulting mechanical forces. The morphological and functional response of non-cancer-derived porcine epithelial cell lines IPEC-1 and IPEC-J2 was analyzed. We found that dynamic growth conditions affect morphology in the enterocyte model IPEC-1 but not in IPEC-J2. Changes in IPEC-1 were accompanied by modifications of the distribution and structure of the F-actin cytoskeleton rather than the amount. The structure of the apical brush border and the tight junction system seemed to be largely unaffected; however, a robust decrease in transepithelial resistance was found in IPEC-1 and partially in IPEC-J2. We further detected an increase in Ki67, pointing towards accelerated proliferation. In line with this finding, we detected a doubling of cellular mitochondrial respiration, which was not linked to a general increase in the respiratory chain capacity. Dynamic cultivation of confluent epithelial cell layers did not evoke signs of senescence. In summary, we identified the mechanical load cycle as a relevant parameter for the modulation of the morphological structure and physiological behaviour of intestinal epithelial cells.