Substrate Stiffness Regulates PDGF-Induced Circular Dorsal Ruffle Formation Through MLCK

As atherosclerosis progresses, vascular smooth muscle cells (VSMCs) invade from the medial layer into the intimal layer and proliferate, contributing to atherosclerotic plaque formation. This migration is stimulated in part by platelet-derived growth factor (PDGF), which is released by endothelial c...

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Bibliographic Details
Published inCellular and molecular bioengineering Vol. 6; no. 2; pp. 138 - 147
Main Authors Huynh, John, Bordeleau, Francois, Kraning-Rush, Casey M., Reinhart-King, Cynthia A.
Format Journal Article
LanguageEnglish
Published Boston Springer US 01.06.2013
Springer Nature B.V
Subjects
Atherosclerosis
Bioengineering
Biological and Medical Physics
Biomaterials
Biomedical Engineering and Bioengineering
Biomedical Engineering/Biotechnology
Biophysics
Cell adhesion & migration
Cell Biology
Cellular
Engineering
Kinases
Migration
Proteins
Signal transduction
Stiffening
Stiffness
Stimulation
Vessels
Traction force
Actin
Cell migration
Vascular smooth muscle cells
Cell contractility
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Summary:As atherosclerosis progresses, vascular smooth muscle cells (VSMCs) invade from the medial layer into the intimal layer and proliferate, contributing to atherosclerotic plaque formation. This migration is stimulated in part by platelet-derived growth factor (PDGF), which is released by endothelial cells and inflammatory cells, and vessel stiffening, which occurs with age and atherosclerosis progression. PDGF induces the formation of circular dorsal ruffles (CDRs), actin-based structures associated with increased cell motility. Here we show that mechanical changes in matrix stiffness enhance the formation of CDRs in VSMCs in response to PDGF stimulation. Our data indicate that matrix stiffness increases cellular contractility, and that intracellular pre-stress is necessary for robust CDR formation. When treated with agonists that promote contractility, cells increase CDR formation, whereas agonists that inhibit contractility lead to decreased CDR formation. Substrate stiffness promotes CDR formation in response to PDGF by upregulating Src activity through myosin light chain kinase. Together, these data indicate that vessel stiffening accompanying atherogenesis may exacerbate VSMC response to PDGF leading to CDR formation.
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ISSN:1865-5025
1865-5033
DOI:10.1007/s12195-013-0278-7