The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics

Persistent Link:
http://hdl.handle.net/10150/626576
Title:
The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics
Author:
Wang, X.; Wang, L.; Garcia, J. G. N.; Dudek, S. M.; Shekhawat, G. S.; Dravid, V. P.
Affiliation:
Univ Arizona, Dept Med
Issue Date:
2018-01-17
Publisher:
NATURE PUBLISHING GROUP
Citation:
The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics 2018, 8 (1) Scientific Reports
Journal:
Scientific Reports
Rights:
© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License.
Collection Information:
This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.
Abstract:
Exploration of human pulmonary artery endothelial cell (EC) as a prototypical biomechanical system has important pathophysiologic relevance because this cell type plays a key role in the development of a wide variety of clinical conditions. The complex hierarchical organization ranging from the molecular scale up to the cellular level has an intimate and intricate relationship to the barrier function between lung tissue and blood. To understand the innate molecule-cell-tissue relationship across varied length-scales, the functional role of c-Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier-altering agonists was investigated using atomic force microscopy. Concurrently, the spatially specific arrangement of cytoskeleton structure and dynamic distribution of critical proteins were examined using scanning electron microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA attenuates both thrombin-and sphingosine 1-phosphate (S1P)-mediated structural changes in ECs, specifically spatially-defined changes in elastic modulus and distribution of critical proteins. These results indicate that c-Abl kinase is an important determinant of cortical actin-based cytoskeletal rearrangement. Our findings directly bridge the gap between kinase activity, structural complexity, and functional connectivity across varied length-scales, and suggest that manipulation of c-Abl kinase activity may be a potential target for the treatment of pulmonary barrier disorders.
ISSN:
2045-2322
PubMed ID:
29343719
DOI:
10.1038/s41598-018-19423-w
Version:
Final published version
Sponsors:
Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSF NNCI1542205]; MRSEC program at the Materials Research Center [NSF DMR-1121262]; International Institute for Nanotechnology (IIN); Keck Foundation; State of Illinois, through the IIN; National Science Foundation [1256188]; National Heart Lung Blood Institute NIH grant [P01 HL 126609, R56 HL HL56088144-06A]; National Natural Science Foundation of China [31700812]
Additional Links:
http://www.nature.com/articles/s41598-018-19423-w

Full metadata record

DC FieldValue Language
dc.contributor.authorWang, X.en
dc.contributor.authorWang, L.en
dc.contributor.authorGarcia, J. G. N.en
dc.contributor.authorDudek, S. M.en
dc.contributor.authorShekhawat, G. S.en
dc.contributor.authorDravid, V. P.en
dc.date.accessioned2018-02-12T21:57:32Z-
dc.date.available2018-02-12T21:57:32Z-
dc.date.issued2018-01-17-
dc.identifier.citationThe Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics 2018, 8 (1) Scientific Reportsen
dc.identifier.issn2045-2322-
dc.identifier.pmid29343719-
dc.identifier.doi10.1038/s41598-018-19423-w-
dc.identifier.urihttp://hdl.handle.net/10150/626576-
dc.description.abstractExploration of human pulmonary artery endothelial cell (EC) as a prototypical biomechanical system has important pathophysiologic relevance because this cell type plays a key role in the development of a wide variety of clinical conditions. The complex hierarchical organization ranging from the molecular scale up to the cellular level has an intimate and intricate relationship to the barrier function between lung tissue and blood. To understand the innate molecule-cell-tissue relationship across varied length-scales, the functional role of c-Abl kinase in the cytoskeletal nano-biomechanics of ECs in response to barrier-altering agonists was investigated using atomic force microscopy. Concurrently, the spatially specific arrangement of cytoskeleton structure and dynamic distribution of critical proteins were examined using scanning electron microscopy and immunofluorescence. Reduction in c-Abl expression by siRNA attenuates both thrombin-and sphingosine 1-phosphate (S1P)-mediated structural changes in ECs, specifically spatially-defined changes in elastic modulus and distribution of critical proteins. These results indicate that c-Abl kinase is an important determinant of cortical actin-based cytoskeletal rearrangement. Our findings directly bridge the gap between kinase activity, structural complexity, and functional connectivity across varied length-scales, and suggest that manipulation of c-Abl kinase activity may be a potential target for the treatment of pulmonary barrier disorders.en
dc.description.sponsorshipSoft and Hybrid Nanotechnology Experimental (SHyNE) Resource [NSF NNCI1542205]; MRSEC program at the Materials Research Center [NSF DMR-1121262]; International Institute for Nanotechnology (IIN); Keck Foundation; State of Illinois, through the IIN; National Science Foundation [1256188]; National Heart Lung Blood Institute NIH grant [P01 HL 126609, R56 HL HL56088144-06A]; National Natural Science Foundation of China [31700812]en
dc.language.isoenen
dc.publisherNATURE PUBLISHING GROUPen
dc.relation.urlhttp://www.nature.com/articles/s41598-018-19423-wen
dc.rights© The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License.en
dc.titleThe Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanicsen
dc.typeArticleen
dc.contributor.departmentUniv Arizona, Dept Meden
dc.identifier.journalScientific Reportsen
dc.description.collectioninformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen

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