The Significant Role of c-Abl Kinase in Barrier Altering Agonists-mediated Cytoskeletal Biomechanics
Year: 2018
Type: article
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.
Source: Scientific Reports
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,690
Funders: National Science Foundation, W. M. Keck Foundation, Northwestern University, National Natural Science Foundation of China, National Institutes of Health, Materials Research Science and Engineering Center, Harvard University, International Institute for Nanotechnology, Northwestern University, National Heart, Lung, and Blood Institute, National Institute of Environmental Health Sciences, Division of Materials Research
Awards: G1179596829, G1893355312, G2379832748, G255020052, G318734614, G3365584222, G3670218291, IDBR: Development of Higher Eigenmode Ultrasound Bioprobe for Sub-Cellular Biological Imaging, G4573007502, G4712878820, G5335290279, NNCI: Soft and Hybrid Nanotechnology Experimental (SHyNE) Resource, G6066762027, G7178204, Cytoskeletal Regulation of Lung Endothelial Pathobiology, CEMRI: Multifunctional Nanoscale Material Structures, Southwest Environmental Health Sciences Center, Cytoskeletal Regulation of Lung Endothelial Pathobiology in ARDS
OpenAlex ID: W2784028322