Dataset Information

Hydrogel micropillars with integrin selective peptidomimetic functionalized nanopatterned tops: a new tool for the measurement of cell traction forces transmitted through αvβ3- or α5β1-integrins.

ABSTRACT: Poly(ethylene glycol) micropillars with gold nanopatterns on top are functionalized with two integrin selective ligands. This platform is a powerful new tool to determine the specific contribution of traction forces involved in cell adhesion mediated by α5β1- and αvβ3-integrins. Cells adherent via α5β1-integrins have a tendency to exert higher maximum forces than cells adhering via αvβ3-integrins.

SUBMITTER: Rahmouni S

PROVIDER: S-EPMC3915041 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Hydrogel micropillars with integrin selective peptidomimetic functionalized nanopatterned tops: a new tool for the measurement of cell traction forces transmitted through αvβ3- or α5β1-integrins.

Rahmouni Sabri S Lindner Aaron A Rechenmacher Florian F Neubauer Stefanie S Sobahi Tariq Rashad Ali TR Kessler Horst H Cavalcanti-Adam Elisabetta Ada EA Spatz Joachim Pius JP

Advanced materials (Deerfield Beach, Fla.) 20130805 41

Poly(ethylene glycol) micropillars with gold nanopatterns on top are functionalized with two integrin selective ligands. This platform is a powerful new tool to determine the specific contribution of traction forces involved in cell adhesion mediated by α5β1- and αvβ3-integrins. Cells adherent via α5β1-integrins have a tendency to exert higher maximum forces than cells adhering via αvβ3-integrins. ...[more]

PMID: 23913640

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Project description:Objective- Alterations in extracellular matrix quantity and composition contribute to atherosclerosis, with remodeling of the subendothelial basement membrane to an FN (fibronectin)-rich matrix preceding lesion development. Endothelial cell interactions with FN prime inflammatory responses to a variety of atherogenic stimuli; however, the mechanisms regulating early atherogenic FN accumulation remain unknown. We previously demonstrated that oxLDL (oxidized low-density lipoprotein) promotes endothelial proinflammatory gene expression by activating the integrin α5β1, a classic mediator of FN fibrillogenesis. Approach and Results- We now show that oxLDL drives robust endothelial FN deposition and inhibiting α5β1 (blocking antibodies, α5 knockout cells) completely inhibits oxLDL-induced FN deposition. Consistent with this, inducible endothelial-specific α5 integrin deletion in ApoE knockout mice significantly reduces atherosclerotic plaque formation, associated with reduced early atherogenic inflammation. Unlike TGFβ (transforming growth factor β)-induced FN deposition, oxLDL does not induce FN expression (mRNA, protein) or the endothelial-to-mesenchymal transition phenotype. In addition, we show that cell-derived and plasma-derived FN differentially affect endothelial function, with only cell-derived FN capable of supporting oxLDL-induced VCAM-1 (vascular cell adhesion molecule 1) expression, despite plasma FN deposition by oxLDL. The inclusion of alternative exon EIIIA (EDA) of FN (EIIIA) and alternative exon EIIIB (EDB) of FN (EIIIB) domains in cell-derived FN mediates this effect, as EIIIA/EIIIB knockout endothelial cells show diminished oxLDL-induced inflammation. Furthermore, our data suggest that EIIIA/EIIIB-positive cellular FN is required for maximal α5β1 recruitment to focal adhesions and FN fibrillogenesis. Conclusions- Taken together, our data demonstrate that endothelial α5 integrins drive oxLDL-induced FN deposition and early atherogenic inflammation. Additionally, we show that α5β1-dependent endothelial FN deposition mediates oxLDL-dependent endothelial inflammation and FN fibrillogenesis.

Dataset Information

Hydrogel micropillars with integrin selective peptidomimetic functionalized nanopatterned tops: a new tool for the measurement of cell traction forces transmitted through αvβ3- or α5β1-integrins.

Publications

Hydrogel micropillars with integrin selective peptidomimetic functionalized nanopatterned tops: a new tool for the measurement of cell traction forces transmitted through αvβ3- or α5β1-integrins.

Similar Datasets

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