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Capturing and Quantifying Particle Transcytosis with Microphysiological Intestine-on-Chip Models
Ludivine C Delon1,2, Matthew Faria3, Zhengyang Jia1,2
1Future Industries Institute, University of South Australia, Adelaide, SA, 5095, Australia.
Small Methods
|December 22, 2022
Summary
Mechanical stimulation significantly enhances intestinal particle transport across Caco-2 cell monolayers. This intestine-on-chip model reveals a 350x higher transcytosis rate, crucial for drug delivery and environmental particle risk assessment.
Area of Science:
- Biomedical Engineering
- Cell Biology
- Pharmacology
Background:
- Intestinal particle transport is vital for drug delivery and understanding environmental risks.
- Caco-2 cell monolayers are standard models but lack polarized enterocyte transcytotic activity.
Purpose of the Study:
- To investigate the effect of mechanical stimulation on intestinal particle transport using an intestine-on-chip model.
- To compare particle transcytosis in static vs. fluid shear stress conditions.
Main Methods:
- Utilized an intestine-on-chip microphysiological system combined with in silico modeling.
- Exposed Caco-2 cell monolayers to fluid shear stress and compared to static cultures.
- Analyzed transcytosis rates, energy dependence, and endocytic pathways (clathrin, macropinocytosis).
Main Results:
- Fluid shear stress increased Caco-2 cell transcytosis by approximately 350x compared to static conditions.
- Mechanical stimulation induced profound phenotypical alterations and a highly polarized cell state.
- Transcytosis was energy-dependent, involving clathrin and macropinocytosis.
- Increased transcytosis was attributed to enhanced internal particle transport (trafficking, exocytosis), not apical uptake.
Conclusions:
- Mechanical stimulation via fluid shear stress dramatically enhances intestinal particle transcytosis in Caco-2 cells.
- The intestine-on-chip model reveals key mechanisms of particle transport, including energy dependence and specific endocytic pathways.
- Findings are critical for optimizing intestinal drug delivery and assessing risks from engineered and environmental particles.
