Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion
- PMID: 15669099
- DOI: 10.1002/jcp.20274
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion
Abstract
Increasing evidence suggests that mechanical cues inherent to the extracellular matrix (ECM) may be equally as critical as its chemical identity in regulating cell behavior. We hypothesized that the mechanical properties of the ECM directly regulate the motility of vascular smooth muscle cells (SMCs) and tested this hypothesis using polyacrylamide substrates with tunable mechanical properties. Quantification of the migration speed on uniformly compliant hydrogels spanning a range of stiffnesses (Young's moduli values from 1.0 to 308 kPa for acrylamide/bisacrylamide ratios between 5/0.1% and 15/1.2%, respectively) revealed a biphasic dependence on substrate compliance, suggesting the existence of an optimal substrate stiffness capable of supporting maximal migration. The value of this optimal stiffness shifted depending on the concentration of ECM protein covalently attached to the substrate. Specifically, on substrates presenting a theoretical density of 0.8 microg/cm(2) fibronectin, the maximum speed of 0.74 +/- 0.09 microm/min was achieved on a 51.9 kPa gel; on substrates presenting a theoretical density of 8.0 microg/cm(2) fibronectin, the maximum speed of 0.72 +/- 0.06 microm/min occurred on a softer 21.6 kPa gel. Pre-treatment of cells with Y27632, an inhibitor of the Rho/Rho-kinase (ROCK) pathway, reduced these observed maxima to values comparable to those on non-optimal stiffnesses. In parallel, quantification of TritonX-insoluble vinculin via Western blotting, coupled with qualitative fluorescent microscopy, revealed that the formation of focal adhesions and actin stress fibers also depends on ECM stiffness. Combined, these data suggest that the mechanical properties of the underlying ECM regulate Rho-mediated contractility in SMCs by disrupting a presumptive cell-ECM force balance, which in turn regulates cytoskeletal assembly and ultimately, cell migration.
(c) 2004 Wiley-Liss, Inc.
Similar articles
-
Induction of the myofibroblastic phenotype in human gingival fibroblasts by transforming growth factor-beta1: role of RhoA-ROCK and c-Jun N-terminal kinase signaling pathways.J Periodontal Res. 2006 Oct;41(5):418-25. doi: 10.1111/j.1600-0765.2006.00886.x. J Periodontal Res. 2006. PMID: 16953819
-
Mechanical forces alter zyxin unbinding kinetics within focal adhesions of living cells.J Cell Physiol. 2006 Apr;207(1):187-94. doi: 10.1002/jcp.20550. J Cell Physiol. 2006. PMID: 16288479
-
ROCK inhibition with Y27632 activates astrocytes and increases their expression of neurite growth-inhibitory chondroitin sulfate proteoglycans.Glia. 2007 Mar;55(4):369-84. doi: 10.1002/glia.20466. Glia. 2007. PMID: 17136770
-
Flux at focal adhesions: slippage clutch, mechanical gauge, or signal depot.Sci STKE. 2007 Mar 13;2007(377):pe10. doi: 10.1126/stke.3772007pe10. Sci STKE. 2007. PMID: 17356172 Review.
-
Biochemistry and biomechanics of cell motility.Annu Rev Biomed Eng. 2005;7:105-50. doi: 10.1146/annurev.bioeng.7.060804.100340. Annu Rev Biomed Eng. 2005. PMID: 16004568 Review.
Cited by
-
A homeostatic role of nucleus-actin filament coupling in the regulation of cellular traction forces in fibroblasts.Biomech Model Mechanobiol. 2024 Mar 19. doi: 10.1007/s10237-024-01839-1. Online ahead of print. Biomech Model Mechanobiol. 2024. PMID: 38502433
-
A multiscale theory for spreading and migration of adhesion-reinforced mesenchymal cells.J R Soc Interface. 2023 Dec;20(209):20230317. doi: 10.1098/rsif.2023.0317. Epub 2023 Dec 13. J R Soc Interface. 2023. PMID: 38086406 Free PMC article.
-
Effect of Mechanical Stimuli on the Phenotypic Plasticity of Induced Pluripotent Stem-Cell-Derived Vascular Smooth Muscle Cells in a 3D Hydrogel.ACS Appl Bio Mater. 2023 Dec 18;6(12):5716-5729. doi: 10.1021/acsabm.3c00840. Epub 2023 Nov 30. ACS Appl Bio Mater. 2023. PMID: 38032545 Free PMC article.
-
Survivin as a mediator of stiffness-induced cell cycle progression and proliferation of vascular smooth muscle cells.APL Bioeng. 2023 Oct 30;7(4):046108. doi: 10.1063/5.0150532. eCollection 2023 Dec. APL Bioeng. 2023. PMID: 37915752 Free PMC article.
-
Environmental stiffness restores mechanical homeostasis in vimentin-depleted cells.Sci Rep. 2023 Oct 26;13(1):18374. doi: 10.1038/s41598-023-44835-8. Sci Rep. 2023. PMID: 37884575 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources