Endothelial directed collective migration depends on substrate stiffness via localized myosin contractility and cell-matrix interactions

Journal of Biomechanics
Adam Charles CanverAlisa Morss Clyne

Abstract

Macrovascular endothelial injury, which may be caused by percutaneous intervention, requires endothelial cell directed collective migration to restore an intact endothelial monolayer. While interventions are often performed in arteries stiffened by cardiovascular disease, the effect of substrate stiffness on endothelial cell collective migration has not been examined. We studied porcine aortic endothelial cell directed collective migration using a modified cage assay on 4, 14, and 50kPa collagen-coated polyacrylamide gels. Total cell migration distance was measured over time, as were nuclear alignment and nuclear:total β-catenin as measures of cell directedness and cell-cell junction integrity, respectively. In addition, fibronectin fibers were examined as a measure of extracellular matrix deposition and remodeling. We now show that endothelial cells collectively migrate farther on stiffer substrates by 24h. Cells were more directed in the migration direction on intermediate stiffness substrates from 12 to 24h, with an alignment peak 400-700µm back from the migratory interface. However, cells on the softest substrates had the highest cell-cell junction integrity. Cells on all substrates deposited fibronectin, however fibronecti...Continue Reading

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Citations

Nov 12, 2016·BioMed Research International·Jean-Michel BourgetRaphaël Devillard
Feb 24, 2017·Microscopy and Microanalysis : the Official Journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada·Adam C Canver, Alisa Morss Clyne
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Aug 13, 2018·ACS Biomaterials Science & Engineering·Michael G McCoyClaudia Fischbach

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