Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/137315
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Type: | Journal article |
Title: | Capturing and Quantifying Particle Transcytosis with Microphysiological Intestine-on-Chip Models |
Author: | Delon, L.C. Faria, M. Jia, Z. Johnston, S. Gibson, R. Prestidge, C.A. Thierry, B. |
Citation: | Small Methods, 2023; 7(1):1-12 |
Publisher: | Wiley |
Issue Date: | 2023 |
ISSN: | 2366-9608 2366-9608 |
Statement of Responsibility: | Ludivine C. Delon, Matthew Faria, Zhengyang Jia, Stuart Johnston, Rachel Gibson, Clive A. Prestidge, and Benjamin Thierry |
Abstract: | Understanding the intestinal transport of particles is critical in several fields ranging from optimizing drug delivery systems to capturing health risks from the increased presence of nano- and micro-sized particles in human environment. While Caco-2 cell monolayers grown on permeable supports are the traditional in vitro model used to probe intestinal absorption of dis-solved molecules, they fail to recapitulate the transcytotic activity of polar-ized enterocytes. Here, an intestine-on-chip model is combined with in silico modeling to demonstrate that the rate of particle transcytosis is ≈350× higher across Caco-2 cell monolayers exposed to fluid shear stress compared to Caco-2 cells in standard “static” configuration. This relates to profound phe-notypical alterations and highly polarized state of cells grown under mechan-ical stimulation and it is shown that transcytosis in the microphysiological model is energy-dependent and involves both clathrin and macropinocytosis mediated endocytic pathways. Finally, it is demonstrated that the increased rate of transcytosis through cells exposed to flow is explained by a higher rate of internal particle transport (i.e., vesicular cellular trafficking and baso-lateral exocytosis), rather than a change in apical uptake (i.e., binding and endocytosis). Taken together, the findings have important implications for addressing research questions concerning intestinal transport of engineered and environmental particles. |
Keywords: | cellular transcytosis enterocytes intestinal absorption intestine-on-chip |
Rights: | © 2022 The Authors. Small Methods published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purpose. |
DOI: | 10.1002/smtd.202200989 |
Grant ID: | http://purl.org/au-research/grants/arc/LP150100032 |
Published version: | http://dx.doi.org/10.1002/smtd.202200989 |
Appears in Collections: | Molecular and Biomedical Science publications |
Files in This Item:
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hdl_137315.pdf | Published version | 2.28 MB | Adobe PDF | View/Open |
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