Regulation of SMC traction forces in human aortic thoracic aneurysms.
Ascending thoracic aortic aneurysm (ataa)
Cell biomechanics
Mechanotransduction
Single cell
Smooth muscle cells (smc)
Traction force microscopy (tfm)
Journal
Biomechanics and modeling in mechanobiology
ISSN: 1617-7940
Titre abrégé: Biomech Model Mechanobiol
Pays: Germany
ID NLM: 101135325
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
28
10
2019
accepted:
12
12
2020
pubmed:
16
1
2021
medline:
4
11
2021
entrez:
15
1
2021
Statut:
ppublish
Résumé
Smooth muscle cells (SMCs) usually express a contractile phenotype in the healthy aorta. However, aortic SMCs have the ability to undergo profound changes in phenotype in response to changes in their extracellular environment, as occurs in ascending thoracic aortic aneurysms (ATAA). Accordingly, there is a pressing need to quantify the mechanobiological effects of these changes at single cell level. To address this need, we applied Traction Force Microscopy (TFM) on 759 cells coming from three primary healthy (AoPrim) human SMC lineages and three primary aneurysmal (AnevPrim) human SMC lineages, from age and gender matched donors. We measured the basal traction forces applied by each of these cells onto compliant hydrogels of different stiffness (4, 8, 12, 25 kPa). Although the range of force generation by SMCs suggested some heterogeneity, we observed that: 1. the traction forces were significantly larger on substrates of larger stiffness; 2. traction forces in AnevPrim were significantly higher than in AoPrim cells. We modelled computationally the dynamic force generation process in SMCs using the motor-clutch model and found that it accounts well for the stiffness-dependent traction forces. The existence of larger traction forces in the AnevPrim SMCs were related to the larger size of cells in these lineages. We conclude that phenotype changes occurring in ATAA, which were previously known to reduce the expression of elongated and contractile SMCs (rendering SMCs less responsive to vasoactive agents), tend also to induce stronger SMCs. Future work aims at understanding the causes of this alteration process in aortic aneurysms.
Identifiants
pubmed: 33449277
doi: 10.1007/s10237-020-01412-6
pii: 10.1007/s10237-020-01412-6
pmc: PMC7979631
doi:
Substances chimiques
Collagen
9007-34-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
717-731Subventions
Organisme : European Research Council
ID : Biolochanics, grant number 647067
Pays : International
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