Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-5-4
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Acrylic Resins, http://linkedlifedata.com/resource/pubmed/chemical/Amides, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Fibronectins, http://linkedlifedata.com/resource/pubmed/chemical/Hydrogel, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Polymers, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Pyridines, http://linkedlifedata.com/resource/pubmed/chemical/Y 27632, http://linkedlifedata.com/resource/pubmed/chemical/polyacrylamide, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
(c) 2004 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
204
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
198-209
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:15669099-Acrylic Resins, pubmed-meshheading:15669099-Actin Cytoskeleton, pubmed-meshheading:15669099-Amides, pubmed-meshheading:15669099-Aorta, pubmed-meshheading:15669099-Blotting, Western, pubmed-meshheading:15669099-Cell Movement, pubmed-meshheading:15669099-Cells, Cultured, pubmed-meshheading:15669099-Elasticity, pubmed-meshheading:15669099-Enzyme Inhibitors, pubmed-meshheading:15669099-Extracellular Matrix, pubmed-meshheading:15669099-Fibronectins, pubmed-meshheading:15669099-Fluorescent Antibody Technique, pubmed-meshheading:15669099-Focal Adhesions, pubmed-meshheading:15669099-Humans, pubmed-meshheading:15669099-Hydrogel, pubmed-meshheading:15669099-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:15669099-Muscle, Smooth, Vascular, pubmed-meshheading:15669099-Polymers, pubmed-meshheading:15669099-Protein-Serine-Threonine Kinases, pubmed-meshheading:15669099-Pyridines, pubmed-meshheading:15669099-Stress, Mechanical, pubmed-meshheading:15669099-rho-Associated Kinases
pubmed:year
2005
pubmed:articleTitle
Extracellular matrix rigidity governs smooth muscle cell motility in a biphasic fashion.
pubmed:affiliation
Department of Chemical Engineering and Materials Science, The Henry Samueli School of Engineering, University of California, Irvine, California, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't