Imatinib Alters Agonists-mediated Cytoskeletal Biomechanics in Lung Endothelium

Scientific Reports
X WangVinayak P Dravid

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 sugges...Continue Reading

References

Oct 19, 2001·Oncogene·M D Schaller
Sep 24, 2004·Physiological Reviews·Michael C Brown, Christopher E Turner
Jun 2, 2005·Circulation·Douglas L Mann, Michael R Bristow
Oct 4, 2005·The Journal of Clinical Investigation·Ralph Theo SchermulyFriedrich Grimminger
Dec 24, 2005·Physiological Reviews·Dolly Mehta, Asrar B Malik
Jul 11, 2008·Cell Motility and the Cytoskeleton·Amanda Gatesman Ammer, Scott A Weed
Jul 29, 2008·Biochemical and Biophysical Research Communications·Q S LiC T Lim
Jan 15, 2010·Recent Results in Cancer Research. Fortschritte Der Krebsforschung. Progrès Dans Les Recherches Sur Le Cancer·Cornelius F Waller
Jun 24, 2011·Science Translational Medicine·Neil M GoldenbergWarren L Lee
Sep 24, 2008·Nanotechnology·Sarah E CrossJames K Gimzewski
Oct 27, 2011·Nature Reviews. Cardiology·Norbert FreyHugo A Katus
Jul 24, 2012·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Michael A Gimbrone, Guillermo García-Cardeña
Oct 23, 2012·Nature Nanotechnology·Marija PlodinecCora-Ann Schoenenberger
Apr 13, 2013·Cardiovascular Research·Imo E HoeferMat J A P Daemen
Dec 7, 2014·American Journal of Physiology. Lung Cellular and Molecular Physiology·E LetsiouS M Dudek
Mar 31, 2015·Arteriosclerosis, Thrombosis, and Vascular Biology·Alicia N RizzoSteven M Dudek

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Methods Mentioned

BETA
atomic force microscopy
scanning electron microscopy
confocal
AFM
force measurements
electron microscopy
confocal microscopy

Software Mentioned

Adobe Photoshop
PeakForce
MATLAB
NIH ImageJ
Zen
ImageJ

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