Journal article
Effect of spatial heterogeneity and colocalization of eNOS and capacitative calcium entry channels on shear stress-induced NO production by endothelial cells: A modeling approach
Cellular and molecular bioengineering, v 11(2)
Apr 2018
PMID: 30288177
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Colocalization of endothelial nitric oxide synthase (eNOS) and capacitative Ca
entry (CCE) channels in microdomains such as cavaeolae in endothelial cells (ECs) has been shown to significantly affect intracellular Ca
dynamics and NO production, but the effect has not been well quantified.
We developed a two-dimensional continuum model of an EC integrating shear stress-mediated ATP production, intracellular Ca
mobilization, and eNOS activation to investigate the effects of spatial colocalization of plasma membrane eNOS and CCE channels on Ca
dynamics and NO production in response to flow-induced shear stress. Our model examines the hypothesis that subcellular colocalization of cellular components can be critical for optimal coupling of NO production to blood flow.
Our simulations predict that heterogeneity of CCE can result in formation of microdomains with significantly higher Ca
compared to the average cytosolic Ca
. Ca
buffers with lower or no mobility further enhanced Ca
gradients relative to mobile buffers. Colocalization of eNOS to CCE channels significantly increased NO production.
Our results provide quantitative understanding for the role of spatial heterogeneity and the compartmentalization of signals in regulation of shear stress-induced NO production.
Metrics
Details
- Title
- Effect of spatial heterogeneity and colocalization of eNOS and capacitative calcium entry channels on shear stress-induced NO production by endothelial cells: A modeling approach
- Creators
- Kenneth A Barbee - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St. Philadelphia, PA, USA 19104Jaimit B Parikh - IBM Thomas J. Watson Research Center, 1101 Kitchawan Rd, Yorktown Heights, NY, USA 10598Yien Liu - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St. Philadelphia, PA, USA 19104Donald G Buerk - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St. Philadelphia, PA, USA 19104Dov Jaron - School of Biomedical Engineering, Science and Health Systems, Drexel University, 3140 Market St. Philadelphia, PA, USA 19104
- Publication Details
- Cellular and molecular bioengineering, v 11(2)
- Publisher
- Springer Nature; United States
- Grant note
- U01 HL116256 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems; [Retired Faculty]
- Web of Science ID
- WOS:000428935100005
- Scopus ID
- 2-s2.0-85044244772
- Other Identifier
- 991014877689704721
UN Sustainable Development Goals (SDGs)
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InCites Highlights
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Biophysics
- Cell & Tissue Engineering
- Cell Biology
- Engineering, Biomedical