Isolated nuclei stiffen in response to low intensity vibration.
LINC complex
Low intensity vibration
Mechanical signal
Mesenchymal stem cells
Nucleus
Journal
Journal of biomechanics
ISSN: 1873-2380
Titre abrégé: J Biomech
Pays: United States
ID NLM: 0157375
Informations de publication
Date de publication:
09 10 2020
09 10 2020
Historique:
received:
16
04
2020
revised:
20
08
2020
accepted:
21
08
2020
pubmed:
16
9
2020
medline:
15
5
2021
entrez:
15
9
2020
Statut:
ppublish
Résumé
The nucleus, central to all cellular activity, relies on both direct mechanical input and its molecular transducers to sense and respond to external stimuli. While it has been shown that isolated nuclei can adapt to applied force ex vivo, the mechanisms governing nuclear mechanoadaptation in response to physiologic forces in vivo remain unclear. To investigate nuclear mechanoadaptation in cells, we developed an atomic force microscopy (AFM) based procedure to probe live nuclei isolated from mesenchymal stem cells (MSCs) following the application of low intensity vibration (LIV) to determine whether nuclear stiffness increases as a result of LIV. Results indicated that isolated nuclei were, on average, 30% softer than nuclei tested within intact MSCs prior to LIV. When the nucleus was isolated following LIV (0.7 g, 90 Hz, 20 min) applied four times (4×) separated by 1 h intervals, stiffness of isolated nuclei increased 75% compared to non-LIV controls. LIV-induced nuclear stiffening required functional Linker of Nucleoskeleton and Cytoskeleton (LINC) complex, but was not accompanied by increased levels of the nuclear envelope proteins LaminA/C or Sun-2. While depleting LaminA/C or Sun-1&2 resulted in either a 47% or 39% increased heterochromatin to nuclear area ratio in isolated nuclei, the heterochromatin to nuclear area ratio was decreased by 25% in LIV-treated nuclei compared to controls, indicating LIV-induced changes in the heterochromatin structure. Overall, our findings indicate that increased apparent cell stiffness in response to exogenous mechanical challenge of MSCs in the form of LIV is in part retained by increased nuclear stiffness and changes in heterochromatin structure.
Identifiants
pubmed: 32932075
pii: S0021-9290(20)30435-8
doi: 10.1016/j.jbiomech.2020.110012
pmc: PMC7590198
mid: NIHMS1628770
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
110012Subventions
Organisme : NIGMS NIH HHS
ID : P20 GM103408
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109095
Pays : United States
Organisme : NICHD NIH HHS
ID : P2C HD086843
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG059923
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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