Regulation of SMC traction forces in human aortic thoracic aneurysms |
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Authors: | Petit Claudie Karkhaneh Yousefi Ali-Akbar Ben Moussa Olfa Michel Jean-Baptiste Guignandon Alain Avril Stéphane |
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Affiliation: | 1.Mines Saint-Etienne, Université de Lyon, INSERM, U 1059 SAINBIOSE, 42023, Saint-Etienne, France ;2.Université Jean Monnet, Université de Lyon, INSERM, U 1059 SAINBIOSE, 42023, Saint-Etienne, France ;3.UMR 1148, Laboratory for Translational Vascular Science, Xavier Bichat Hospital, Inserm and Paris 7- Denis Diderot University, 75018, Paris, France ; |
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Abstract: | 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. |
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