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Updated: Sep 30, 2025
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An Intravital Microscopy-Based Approach to Assess Intestinal Permeability and Epithelial Cell Shedding Performance
Published on: December 3, 2020
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Simple graphical approach to investigate differences in transepithelial paracellular leak pathway permeability
Ashley Monaco1, Josephine Axis1, Kurt Amsler1
1Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, Old Westbury, New York, USA.
Physiological Reports
|March 11, 2022
Summary
Understanding epithelial barrier function requires distinguishing between changes in pore size and pore density. This study introduces a graphical method to differentiate these factors, revealing ZO-1 depletion alters pore size and density, while ZO-2 depletion has minimal impact.
Area of Science:
- Cell Biology
- Epithelial Physiology
- Computational Biology
Background:
- Epithelial paracellular permeability differences are common but their underlying mechanisms (pore size vs. density) are unclear.
- Distinguishing between these mechanisms is crucial for understanding epithelial barrier function.
Purpose of the Study:
- To develop and validate a computational approach to distinguish between changes in epithelial Leak Pathway opening size and density.
- To apply this method to analyze the effects of ZO-1 and ZO-2 protein depletion and compare different cell types.
Main Methods:
- Utilized a computational approach comparing apparent paracellular permeabilities of various sized solutes across different cell layers.
- Quantified changes in Leak Pathway opening size and density in response to protein depletion and cell type differences.
Main Results:
- Depletion of ZO-1 in MDCK Type II cells decreased opening size and increased opening density.
- Depletion of ZO-2 had minimal effect on opening size and density.
- MDCK Type I cells showed lower permeability than Type II cells due to decreased opening density.
Conclusions:
- The developed graphical method effectively distinguishes between changes in epithelial Leak Pathway opening size and density.
- ZO-1 and ZO-2 proteins play distinct roles in regulating epithelial barrier permeability.
- This approach offers broad applications for analyzing factors influencing epithelial permeability.
