Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Altered Mesenchymal Stem Cells Mechanotransduction from Oxidized Collagen. Morphological and Biophysical Observations

Regina Komsa-Penkova
* ORCID logo ,
Adelina Yordanova
,
Pencho Tonchev
,
Stanimir Kyurkchiev
,
Svetla Todinova
ORCID logo ,
Velichka Strijkova
,
Mario Iliev
,
Borislav Dimitrov
,
Altankov George
*
Version 1 : Received: 8 January 2023 / Approved: 9 January 2023 / Online: 9 January 2023 (09:53:23 CET)

A peer-reviewed article of this Preprint also exists.

Komsa-Penkova, R.; Yordanova, A.; Tonchev, P.; Kyurkchiev, S.; Todinova, S.; Strijkova, V.; Iliev, M.; Dimitrov, B.; Altankov, G. Altered Mesenchymal Stem Cells Mechanotransduction from Oxidized Collagen: Morphological and Biophysical Observations. Int. J. Mol. Sci. 2023, 24, 3635. Komsa-Penkova, R.; Yordanova, A.; Tonchev, P.; Kyurkchiev, S.; Todinova, S.; Strijkova, V.; Iliev, M.; Dimitrov, B.; Altankov, G. Altered Mesenchymal Stem Cells Mechanotransduction from Oxidized Collagen: Morphological and Biophysical Observations. Int. J. Mol. Sci. 2023, 24, 3635.

Abstract

ECM provides various mechanical cues that are able to affect the self‑renewal and differentiation of mesenchymal stem cells (MSC). Little is known however how these ques work in a pathological environment, such as acute oxidative stress. To better understand the behavior of human adipose tissue-derived MSC (ADMSC) in such conditions here we provide morphological and quantitative evidence for significantly altered early steps of mechanotransduction when adhering to oxidized collagen (Col-Oxi). This affects both focal adhesion (FA) formation and YAP/TAZ signaling events. Representative morphological images show that ADMSCs spread better within 2 h of adhesion on native collagen (Col), while they tended to round up on Col-Oxi. It correlates also with the less development of the actin cytoskeleton and FA formation, confirmed quantitatively by morpho-metric analysis using ImageJ. As shown by immunofluorescence analysis, oxidation also affected the ratio of cytosolic to nuclear YAP/TAZ activity, concentrating in the nucleus for Col while remaining in the cytosol for Col-Oxi, suggesting abrogated signal transduction. Comparative AFM studies show that native collagen forms relatively coarse aggregates, much thinner with Col-Oxi, possibly reflecting its altered ability to aggregate. On the other hand, the corresponding Young's moduli were only slightly changed, so viscoelastic properties cannot explain the observed biological differences. However, the roughness of the protein layer decreases dramatically, from RRMS equal to 27.95 + 5.1 nm for Col to 5.51 + 0.8 nm for Col-Oxi (p<0.05), which dictates our conclusion that it is the most altered parameter in oxidation. Thus, it appears to be a predominantly topo-graphic response that affects the mechanotransduction of ADMSCs by oxidized collagen.

Keywords

mesenchymal stem cells; mechanotransduction; collagen; oxidation; YAP/TAZ; focal adhesion

Subject

Biology and Life Sciences, Cell and Developmental Biology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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