Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium

X. Wang, R. Bleher, L. Wang, Joe GN Garcia, S. M. Dudek, G. S. Shekhawat, V. P. Dravid

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The endothelium serves as a size-selective barrier and tightly controls the fluid exchange from the circulation to the surrounding tissues. In this study, a multiplexed microscopy characterization is developed to study the spatio-temporal effects of Abl kinases on endothelial cytoskeletal structure using AFM, SEM, and immunofluorescence. Sphingosine 1-phosphate (S1P) produces significant endothelial barrier enhancement by means of peripheral actin rearrangement. However, Abl kinase inhibition by imatinib reduces rapid redistribution of the important cytoskeletal proteins to the periphery and their association with the cortical actin ring. Herein, it moderates the thickness of the cortical actin ring, and diminishes the increase in elastic modulus at the periphery and cytoplasm. These findings demonstrate that imatinib attenuates multiple cytoskeletal changes associated with S1P-mediated endothelial barrier enhancement and suggest a novel role for Abl kinases in mediating these S1P effects. These observations bridge the gap between molecule dynamics, structure complexity and function connectivity across varied length-scales to improve our understanding on human pulmonary endothelial barrier regulation. Moreover, our study suggests a framework for understanding form-function relationships in other biomechanical subsystems, wherein complex hierarchical organization programmed from the molecular scale to the cellular and tissue levels has an intimate relationship to the overall physiological function.

Original languageEnglish (US)
Article number14152
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Biomechanical Phenomena
Endothelium
Actins
Phosphotransferases
Lung
Cytoskeletal Proteins
Elastic Modulus
Fluorescent Antibody Technique
Microscopy
Cytoplasm
sphingosine 1-phosphate
Imatinib Mesylate

ASJC Scopus subject areas

  • General

Cite this

Wang, X., Bleher, R., Wang, L., Garcia, J. GN., Dudek, S. M., Shekhawat, G. S., & Dravid, V. P. (2017). Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium. Scientific Reports, 7(1), [14152]. https://doi.org/10.1038/s41598-017-14722-0

Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium. / Wang, X.; Bleher, R.; Wang, L.; Garcia, Joe GN; Dudek, S. M.; Shekhawat, G. S.; Dravid, V. P.

In: Scientific Reports, Vol. 7, No. 1, 14152, 01.12.2017.

Research output: Contribution to journalArticle

Wang, X. ; Bleher, R. ; Wang, L. ; Garcia, Joe GN ; Dudek, S. M. ; Shekhawat, G. S. ; Dravid, V. P. / Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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